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Substrate specificity of Mycobacterium tuberculosis tRNA terminal nucleotidyltransferase toxin MenT3 Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-15 Jun Liu, Yuka Yashiro, Yuriko Sakaguchi, Tsutomu Suzuki, Kozo Tomita
Mycobacterium tuberculosis transfer RNA (tRNA) terminal nucleotidyltransferase toxin, MenT3, incorporates nucleotides at the 3′-CCA end of tRNAs, blocking their aminoacylation and inhibiting protein synthesis. Here, we show that MenT3 most effectively adds CMPs to the 3′-CCA end of tRNA. The crystal structure of MenT3 in complex with CTP reveals a CTP-specific nucleotide-binding pocket. The 4-NH2 and
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Molecular mechanism of the one-component regulator RccR on bacterial metabolism and virulence Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-13 Yibo Zhu, Xingyu Mou, Yingjie Song, Qianqian Zhang, Bo Sun, Huanxiang Liu, Hong Tang, Rui Bao
The regulation of carbon metabolism and virulence is critical for the rapid adaptation of pathogenic bacteria to host conditions. In Pseudomonas aeruginosa, RccR is a transcriptional regulator of genes involved in primary carbon metabolism and is associated with bacterial resistance and virulence, although the exact mechanism is unclear. Our study demonstrates that PaRccR is a direct repressor of the
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Catalytic residues of microRNA Argonautes play a modest role in microRNA star strand destabilization in C. elegans Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-13 Kasuen Kotagama, Acadia L Grimme, Leah Braviner, Bing Yang, Rima M Sakhawala, Guoyun Yu, Lars Kristian Benner, Leemor Joshua-Tor, Katherine McJunkin
Many microRNA (miRNA)-guided Argonaute proteins can cleave RNA (‘slicing’), even though miRNA-mediated target repression is generally cleavage-independent. Here we use Caenorhabditis elegans to examine the role of catalytic residues of miRNA Argonautes in organismal development. In contrast to previous work, mutations in presumed catalytic residues did not interfere with development when introduced
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Comprehensive transcriptome analysis reveals altered mRNA splicing and post-transcriptional changes in the aged mouse brain Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-13 Nisha Hemandhar Kumar, Verena Kluever, Emanuel Barth, Sebastian Krautwurst, Mattia Furlan, Mattia Pelizzola, Manja Marz, Eugenio F Fornasiero
A comprehensive understanding of molecular changes during brain aging is essential to mitigate cognitive decline and delay neurodegenerative diseases. The interpretation of mRNA alterations during brain aging is influenced by the health and age of the animal cohorts studied. Here, we carefully consider these factors and provide an in-depth investigation of mRNA splicing and dynamics in the aging mouse
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Structural basis of how MGME1 processes DNA 5′ ends to maintain mitochondrial genome integrity Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-13 Eric Y C Mao, Han-Yi Yen, Chyuan-Chuan Wu
Mitochondrial genome maintenance exonuclease 1 (MGME1) helps to ensure mitochondrial DNA (mtDNA) integrity by serving as an ancillary 5′-exonuclease for DNA polymerase γ. Curiously, MGME1 exhibits unique bidirectionality in vitro, being capable of degrading DNA from either the 5′ or 3′ end. The structural basis of this bidirectionally and, particularly, how it processes DNA from the 5′ end to assist
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CRISPR antiphage defence mediated by the cyclic nucleotide-binding membrane protein Csx23 Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-13 Sabine Grüschow, Stuart McQuarrie, Katrin Ackermann, Stephen McMahon, Bela E Bode, Tracey M Gloster, Malcolm F White
CRISPR-Cas provides adaptive immunity in prokaryotes. Type III CRISPR systems detect invading RNA and activate the catalytic Cas10 subunit, which generates a range of nucleotide second messengers to signal infection. These molecules bind and activate a diverse range of effector proteins that provide immunity by degrading viral components and/or by disturbing key aspects of cellular metabolism to slow
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DNA fragility at topologically associated domain boundaries is promoted by alternative DNA secondary structure and topoisomerase II activity Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-07 Heather M Raimer Young, Pei-Chi Hou, Anna R Bartosik, Naomi D Atkin, Lixin Wang, Zhenjia Wang, Aakrosh Ratan, Chongzhi Zang, Yuh-Hwa Wang
CCCTC-binding factor (CTCF) binding sites are hotspots of genome instability. Although many factors have been associated with CTCF binding site fragility, no study has integrated all fragility-related factors to understand the mechanism(s) of how they work together. Using an unbiased, genome-wide approach, we found that DNA double-strand breaks (DSBs) are enriched at strong, but not weak, CTCF binding
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Determinant of m6A regional preference by transcriptional dynamics Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-07 Yalan Wang, Shen Wang, Zhen Meng, Xiao-Min Liu, Yuanhui Mao
N6-Methyladenosine (m6A) is the most abundant chemical modification occurring on eukaryotic mRNAs, and has been reported to be involved in almost all stages of mRNA metabolism. The distribution of m6A sites is notably asymmetric along mRNAs, with a strong preference toward the 3′ terminus of the transcript. How m6A regional preference is shaped remains incompletely understood. In this study, by performing
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WSB1/2 target chromatin-bound lysine-methylated RelA for proteasomal degradation and NF-κB termination Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-07 Jie Zhang, Yuanyuan Yu, Xiuqun Zou, Yaning Du, Qiankun Liang, Mengyao Gong, Yurong He, Junqi Luo, Dandan Wu, Xiaoli Jiang, Matt Sinclair, Emad Tajkhorshid, Hong-Zhuan Chen, Zhaoyuan Hou, Yuejuan Zheng, Lin-Feng Chen, Xiao-Dong Yang
Proteasome-mediated degradation of chromatin-bound NF-κB is critical in terminating the transcription of pro-inflammatory genes and can be triggered by Set9-mediated lysine methylation of the RelA subunit. However, the E3 ligase targeting methylated RelA remains unknown. Here, we find that two structurally similar substrate-recognizing components of Cullin-RING E3 ligases, WSB1 and WSB2, can recognize
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Identification of G-quadruplex-interacting proteins in living cells using an artificial G4-targeting biotin ligase Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-07 Ziang Lu, Shengjie Xie, Haomiao Su, Shaoqing Han, Haiyan Huang, Xiang Zhou
G-quadruplexes (G4s) are noncanonical nucleic acid structures pivotal to cellular processes and disease pathways. Deciphering G4-interacting proteins is imperative for unraveling G4’s biological significance. In this study, we developed a G4-targeting biotin ligase named G4PID, meticulously assessing its binding affinity and specificity both in vitro and in vivo. Capitalizing on G4PID, we devised a
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Implication of nucleotides near the 3′ end of 16S rRNA in guarding the translational reading frame Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-07 Alexandria Smart, Laura Lancaster, John Paul Donohue, Dustin Niblett, Harry F Noller
Loss of the translational reading frame leads to misincorporation and premature termination, which can have lethal consequences. Based on structural evidence that A1503 of 16S rRNA intercalates between specific mRNA bases, we tested the possibility that it plays a role in maintenance of the reading frame by constructing ribosomes with an abasic nucleotide at position 1503. This was done by specific
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Set2 regulates Ccp1 and Swc2 to ensure centromeric stability by retargeting CENP-A Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-05 Kim Kiat Lim, Ulysses Tsz Fung Lam, Ying Li, Yi Bing Zeng, Henry Yang, Ee Sin Chen
Precise positioning of the histone-H3 variant, CENP-A, ensures centromere stability and faithful chromosomal segregation. Mislocalization of CENP-A to extra-centromeric loci results in aneuploidy and compromised cell viability associated with formation of ectopic kinetochores. The mechanism that retargets mislocalized CENP-A back to the centromere is unclarified. We show here that the downregulation
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An alphacoronavirus polymerase structure reveals conserved replication factor functions Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-05 Thomas K Anderson, Peter J Hoferle, Kennan J Chojnacki, Kenneth W Lee, Joshua J Coon, Robert N Kirchdoerfer
Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biology comes from betacoronaviruses like SARS-CoV and SARS-CoV-2, the latter of which is the causative agent
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Origin, evolution, and maintenance of gene-strand bias in bacteria Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-05 Malhar Atre, Bharat Joshi, Jebin Babu, Shabduli Sawant, Shreya Sharma, T Sabari Sankar
Gene-strand bias is a characteristic feature of bacterial genome organization wherein genes are preferentially encoded on the leading strand of replication, promoting co-orientation of replication and transcription. This co-orientation bias has evolved to protect gene essentiality, expression, and genomic stability from the harmful effects of head-on replication-transcription collisions. However, the
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Conserved structures and dynamics in 5′-proximal regions of Betacoronavirus RNA genomes Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-01 Tales Rocha de Moura, Elżbieta Purta, Agata Bernat, Eva M Martín-Cuevas, Małgorzata Kurkowska, Eugene F Baulin, Sunandan Mukherjee, Jakub Nowak, Artur P Biela, Michał Rawski, Sebastian Glatt, Fernando Moreno-Herrero, Janusz M Bujnicki
Betacoronaviruses are a genus within the Coronaviridae family of RNA viruses. They are capable of infecting vertebrates and causing epidemics as well as global pandemics in humans. Mitigating the threat posed by Betacoronaviruses requires an understanding of their molecular diversity. The development of novel antivirals hinges on understanding the key regulatory elements within the viral RNA genomes
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Splicing analysis of STAT3 tandem donor suggests non-canonical binding registers for U1 and U6 snRNAs Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-01 Michal Kramárek, Přemysl Souček, Kamila Réblová, Lucie Kajan Grodecká, Tomáš Freiberger
Tandem donor splice sites (5′ss) are unique regions with at least two GU dinucleotides serving as splicing cleavage sites. The Δ3 tandem 5′ss are a specific subclass of 5′ss separated by 3 nucleotides which can affect protein function by inserting/deleting a single amino acid. One 5′ss is typically preferred, yet factors governing particular 5′ss choice are not fully understood. A highly conserved
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Bioorthogonal labeling and profiling of N6-isopentenyladenosine (i6A) modified RNA Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-01 Yuanyuan Li, Hongling Zhou, Shasha Chen, Yinan Li, Yuyang Guo, Xiaoqian Chen, Sheng Wang, Li Wang, Youfang Gan, Shusheng Zhang, Ya Ying Zheng, Jia Sheng, Zhipeng Zhou, Rui Wang
Chemical modifications in RNAs play crucial roles in diversifying their structures and regulating numerous biochemical processes. Since the 1990s, several hydrophobic prenyl-modifications have been discovered in various RNAs. Prenyl groups serve as precursors for terpenes and many other biological molecules. The processes of prenylation in different macromolecules have been extensively studied. We
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Peptide nucleic acid-assisted generation of targeted double-stranded DNA breaks with T7 endonuclease I Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-29 Rashid Aman, Muntjeeb M Syed, Ahmed Saleh, Firdaws Melliti, Sivakrishna Rao Gundra, Qiaochu Wang, Tin Marsic, Ahmed Mahas, Magdy M Mahfouz
Gene-editing technologies have revolutionized biotechnology, but current gene editors suffer from several limitations. Here, we harnessed the power of gamma-modified peptide nucleic acids (γPNAs) to facilitate targeted, specific DNA invasion and used T7 endonuclease I (T7EI) to recognize and cleave the γPNA-invaded DNA. Our data show that T7EI can specifically target PNA-invaded linear and circular
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Characterisation and engineering of a thermophilic RNA ligase from Palaeococcus pacificus Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-29 Meghan Rousseau, Tifany Oulavallickal, Adele Williamson, Vic Arcus, Wayne M Patrick, Joanna Hicks
RNA ligases are important enzymes in molecular biology and are highly useful for the manipulation and analysis of nucleic acids, including adapter ligation in next-generation sequencing of microRNAs. Thermophilic RNA ligases belonging to the RNA ligase 3 family are gaining attention for their use in molecular biology, for example a thermophilic RNA ligase from Methanobacterium thermoautotrophicum is
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The repertoire and structure of adhesion GPCR transcript variants assembled from publicly available deep-sequenced human samples Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-29 Christina Katharina Kuhn, Udo Stenzel, Sandra Berndt, Ines Liebscher, Torsten Schöneberg, Susanne Horn
Alternative splicing and multiple transcription start and termination sites can produce a diverse repertoire of mRNA transcript variants from a given gene. While the full picture of the human transcriptome is still incomplete, publicly available RNA datasets have enabled the assembly of transcripts. Using publicly available deep sequencing data from 927 human samples across 48 tissues, we quantified
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HBO1 determines SMAD action in pluripotency and mesendoderm specification Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-29 Cong Zhang, Yongli Shan, Huaisong Lin, Yanqi Zhang, Qi Xing, Jinmin Zhu, Tiancheng Zhou, Aiping Lin, Qianyu Chen, Junwei Wang, Guangjin Pan
TGF-β signaling family plays an essential role to regulate fate decisions in pluripotency and lineage specification. How the action of TGF-β family signaling is intrinsically executed remains not fully elucidated. Here, we show that HBO1, a MYST histone acetyltransferase (HAT) is an essential cell intrinsic determinant for TGF-β signaling in human embryonic stem cells (hESCs). HBO1−/− hESCs fail to
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Chemical modification patterns for microRNA therapeutic mimics: a structure-activity relationship (SAR) case-study on miR-200c Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-29 Marion Garreau, Julie Weidner, Russell Hamilton, Ewa Kolosionek, Naoko Toki, Kathrin Stavenhagen, Clément Paris, Alessandro Bonetti, Werngard Czechtizky, Felix Gnerlich, Anna Rydzik
microRNA (miRNA) mimics are an emerging class of oligonucleotide therapeutics, with a few compounds already in clinical stages. Synthetic miRNAs are able to restore downregulated levels of intrinsic miRNAs, allowing for parallel regulation of multiple genes involved in a particular disease. In this work, we examined the influence of chemical modifications patterns in miR-200c mimics, assessing the
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CSB and SMARCAL1 compete for RPA32 at stalled forks and differentially control the fate of stalled forks in BRCA2-deficient cells Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-28 Nicole L Batenburg, Dana J Sowa, John R Walker, Sara N Andres, Xu-Dong Zhu
CSB (Cockayne syndrome group B) and SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent, regulator of chromatin, subfamily A-like 1) are DNA translocases that belong to the SNF2 helicase family. They both are enriched at stalled replication forks. While SMARCAL1 is recruited by RPA32 to stalled forks, little is known about whether RPA32 also regulates CSB’s association with stalled forks
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A circular RNA-gawky-chromatin regulatory axis modulates stress-induced transcription Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-28 Rui Su, Min Zhou, Jiamei Lin, Ge Shan, Chuan Huang
In response to heavy metal stress, the RNA-binding protein (RBP) gawky translocates into the nucleus and acts as a chromatin-interacting factor to activate the transcription of many stress-responsive genes. However, the upstream regulators of gawky-mediated transcription and their mechanistic details remain unknown. Here, we identified a class of metal-responsive element-containing circRNAs (MRE circRNAs)
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Novel insights into the role of translesion synthesis polymerase in DNA incorporation and bypass of 5-fluorouracil in colorectal cancer Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-28 Jameson R Averill, Jackson C Lin, John Jung, Hunmin Jung
5-Fluorouracil (5-FU) is the first-line chemotherapeutic agent in colorectal cancer, and resistance to 5-FU easily emerges. One of the mechanisms of drug action and resistance of 5-FU is through DNA incorporation. Our quantitative reverse-transcription PCR data showed that one of the translesion synthesis (TLS) DNA polymerases, DNA polymerase η (polη), was upregulated within 72 h upon 5-FU administration
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Comprehensive map of ribosomal 2′-O-methylation and C/D box snoRNAs in Drosophila melanogaster Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-28 Athena Sklias, Sonia Cruciani, Virginie Marchand, Mariangela Spagnuolo, Guillaume Lavergne, Valérie Bourguignon, Alessandro Brambilla, René Dreos, Steven J Marygold, Eva Maria Novoa, Yuri Motorin, Jean-Yves Roignant
During their maturation, ribosomal RNAs (rRNAs) are decorated by hundreds of chemical modifications that participate in proper folding of rRNA secondary structures and therefore in ribosomal function. Along with pseudouridine, methylation of the 2′-hydroxyl ribose moiety (Nm) is the most abundant modification of rRNAs. The majority of Nm modifications in eukaryotes are placed by Fibrillarin, a conserved
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RNA–RNA interactions between respiratory syncytial virus and miR-26 and miR-27 are associated with regulation of cell cycle and antiviral immunity Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-27 Sarah Ressel, Sujai Kumar, Jose Roberto Bermúdez-Barrientos, Katrina Gordon, Julia Lane, Jin Wu, Cei Abreu-Goodger, Jürgen Schwarze, Amy H Buck
microRNAs (miRNAs) regulate nearly all physiological processes but our understanding of exactly how they function remains incomplete, particularly in the context of viral infections. Here, we adapt a biochemical method (CLEAR-CLIP) and analysis pipeline to identify targets of miRNAs in lung cells infected with Respiratory syncytial virus (RSV). We show that RSV binds directly to miR-26 and miR-27 through
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An engineered baculoviral protein and DNA co-delivery system for CRISPR-based mammalian genome editing Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-27 Julien Capin, Alexandra Harrison, Renata A Raele, Sathish K N Yadav, Dominique Baiwir, Gabriel Mazzucchelli, Loic Quinton, Timothy J Satchwell, Ashley M Toye, Christiane Schaffitzel, Imre Berger, Francesco Aulicino
CRISPR-based DNA editing technologies enable rapid and accessible genome engineering of eukaryotic cells. However, the delivery of genetically encoded CRISPR components remains challenging and sustained Cas9 expression correlates with higher off-target activities, which can be reduced via Cas9-protein delivery. Here we demonstrate that baculovirus, alongside its DNA cargo, can be used to package and
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LC3B drives transcription-associated homologous recombination via direct interaction with R-loops Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-27 Junghyun Yoon, Yiseul Hwang, Hansol Yun, Jee Min Chung, Soyeon Kim, Gyeongmin Kim, Yeji Lee, Byoung Dae Lee, Ho Chul Kang
Exploring the connection between ubiquitin-like modifiers (ULMs) and the DNA damage response (DDR), we employed several advanced DNA damage and repair assay techniques and identified a crucial role for LC3B. Notably, its RNA recognition motif (RRM) plays a pivotal role in the context of transcription-associated homologous recombination (HR) repair (TA-HRR), a particular subset of HRR pathways. Surprisingly
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Structural insights into the N-terminal APHB domain of HrpA: mediating canonical and i-motif recognition Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-27 Ben-Ge Xin, Ling-Yun Huang, Ling-Gang Yuan, Na-Nv Liu, Hai-Hong Li, Xia Ai, Dong-Sheng Lei, Xi-Miao Hou, Stephane Rety, Xu-Guang Xi
RNA helicases function as versatile enzymes primarily responsible for remodeling RNA secondary structures and organizing ribonucleoprotein complexes. In our study, we conducted a systematic analysis of the helicase-related activities of Escherichia coli HrpA and presented the structures of both its apo form and its complex bound with both conventional and non-canonical DNAs. Our findings reveal that
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BISCUIT: an efficient, standards-compliant tool suite for simultaneous genetic and epigenetic inference in bulk and single-cell studies Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-27 Wanding Zhou, Benjamin K Johnson, Jacob Morrison, Ian Beddows, James Eapen, Efrat Katsman, Ayush Semwal, Walid Abi Habib, Lyong Heo, Peter W Laird, Benjamin P Berman, Timothy J Triche, Hui Shen
Data from both bulk and single-cell whole-genome DNA methylation experiments are under-utilized in many ways. This is attributable to inefficient mapping of methylation sequencing reads, routinely discarded genetic information, and neglected read-level epigenetic and genetic linkage information. We introduce the BISulfite-seq Command line User Interface Toolkit (BISCUIT) and its companion R/Bioconductor
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COSA-1 mediated pro-crossover complex formation promotes meiotic crossing over in C. elegans Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-27 Yuejun Yang, Nan Wang, Guoteng Liu, Wencong Nan, Bin Wang, Anton Gartner, Hongtao Zhang, Ye Hong
Accurate chromosome segregation during meiosis requires the establishment of at least one crossover (CO) between each pair of homologous chromosomes. CO formation depends on a group of conserved pro-CO proteins, which colocalize at CO-designated sites during late meiotic prophase I. However, it remains unclear whether these pro-CO proteins form a functional complex and how they promote meiotic CO formation
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UPF1 ATPase autoinhibition and activation modulate RNA binding kinetics and NMD efficiency Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-27 Joseph H Chapman, Alice M Youle, Acadia L Grimme, Keir C Neuman, J Robert Hogg
The RNA helicase UPF1 interacts with mRNAs, mRNA decay machinery, and the terminating ribosome to promote nonsense-mediated mRNA decay (NMD). Structural and biochemical data have revealed that UPF1 exists in an enzymatically autoinhibited ‘closed’ state. Upon binding the NMD protein UPF2, UPF1 undergoes an extensive conformational change into a more enzymatically active ‘open’ state, which exhibits
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Tracking pairwise genomic loci by the ParB–ParS and Noc-NBS systems in living cells Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-27 Xiaohui He, Yuxi Tan, Ying Feng, Yadong Sun, Hanhui Ma
The dynamics of genomic loci pairs and their interactions are essential for transcriptional regulation and genome organization. However, a robust method for tracking pairwise genomic loci in living cells is lacking. Here we developed a multicolor DNA labeling system, mParSpot (multicolor ParSpot), to track pairs of genomic loci and their interactions in living cells. The mParSpot system is derived
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Structural insights into the morpholino nucleic acid/RNA duplex using the new XNA builder Ducque in a molecular modeling pipeline Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-27 Jérôme Rihon, Charles-Alexandre Mattelaer, Rinaldo Wander Montalvão, Mathy Froeyen, Vitor Bernardes Pinheiro, Eveline Lescrinier
The field of synthetic nucleic acids with novel backbone structures [xenobiotic nucleic acids (XNAs)] has flourished due to the increased importance of XNA antisense oligonucleotides and aptamers in medicine, as well as the development of XNA processing enzymes and new XNA genetic materials. Molecular modeling on XNA structures can accelerate rational design in the field of XNAs as it contributes in
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Ribosomal quality control factors inhibit repeat-associated non-AUG translation from GC-rich repeats Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-27 Yi-Ju Tseng, Amy Krans, Indranil Malik, Xiexiong Deng, Evrim Yildirim, Sinem Ovunc, Elizabeth M H Tank, Karen Jansen-West, Ross Kaufhold, Nicolas B Gomez, Roger Sher, Leonard Petrucelli, Sami J Barmada, Peter K Todd
A GGGGCC (G4C2) hexanucleotide repeat expansion in C9ORF72 causes amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), while a CGG trinucleotide repeat expansion in FMR1 leads to the neurodegenerative disorder Fragile X-associated tremor/ataxia syndrome (FXTAS). These GC-rich repeats form RNA secondary structures that support repeat-associated non-AUG (RAN) translation of toxic proteins
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DNA-PKcs suppresses illegitimate chromosome rearrangements Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-27 Jinglong Wang, Cheyenne A Sadeghi, Richard L Frock
Two DNA repair pathways, non-homologous end joining (NHEJ) and alternative end joining (A-EJ), are involved in V(D)J recombination and chromosome translocation. Previous studies reported distinct repair mechanisms for chromosome translocation, with NHEJ involved in humans and A-EJ in mice predominantly. NHEJ depends on DNA-PKcs, a critical partner in synapsis formation and downstream component activation
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The jet-like chromatin structure defines active secondary metabolism in fungi Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-26 Wenyong Shao, Jingrui Wang, Yueqi Zhang, Chaofan Zhang, Jie Chen, Yun Chen, Zhangjun Fei, Zhonghua Ma, Xuepeng Sun, Chen Jiao
Eukaryotic genomes are spatially organized within the nucleus in a nonrandom manner. However, fungal genome arrangement and its function in development and adaptation remain largely unexplored. Here, we show that the high-order chromosome structure of Fusarium graminearum is sculpted by both H3K27me3 modification and ancient genome rearrangements. Active secondary metabolic gene clusters form a structure
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When Paul Berg meets Donald Crothers: an achiral connection through protein biosynthesis Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-26 Pradeep Kumar, Rajan Sankaranarayanan
Outliers in scientific observations are often ignored and mostly remain unreported. However, presenting them is always beneficial since they could reflect the actual anomalies that might open new avenues. Here, we describe two examples of the above that came out of the laboratories of two of the pioneers of nucleic acid research in the area of protein biosynthesis, Paul Berg and Donald Crothers. Their
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Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-26 Rakesh Aithal, Kuldeep Nangalia, Mario Spirek, Doris Chen, Franz Klein, Lumir Krejci
Meiotic recombination is of central importance for the proper segregation of homologous chromosomes, but also for creating genetic diversity. It is initiated by the formation of double-strand breaks (DSBs) in DNA catalysed by evolutionarily conserved Spo11, together with additional protein partners. Difficulties in purifying the Spo11 protein have limited the characterization of its biochemical properties
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Cryptic proteins translated from deletion-containing viral genomes dramatically expand the influenza virus proteome Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-26 Jordan N Ranum, Mitchell P Ledwith, Fadi G Alnaji, Meghan Diefenbacher, Richard Orton, Elizabeth Sloan, Melissa Güereca, Elizabeth M Feltman, Katherine Smollett, Ana da Silva Filipe, Michaela Conley, Alistair B Russell, Christopher B Brooke, Edward Hutchinson, Andrew Mehle
Productive infections by RNA viruses require faithful replication of the entire genome. Yet many RNA viruses also produce deletion-containing viral genomes (DelVGs), aberrant replication products with large internal deletions. DelVGs interfere with the replication of wild-type virus and their presence in patients is associated with better clinical outcomes. The DelVG RNA itself is hypothesized to confer
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Low-input and single-cell methods for Infinium DNA methylation BeadChips Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-26 Sol Moe Lee, Christian E Loo, Rexxi D Prasasya, Marisa S Bartolomei, Rahul M Kohli, Wanding Zhou
The Infinium BeadChip is the most widely used DNA methylome assay technology for population-scale epigenome profiling. However, the standard workflow requires over 200 ng of input DNA, hindering its application to small cell-number samples, such as primordial germ cells. We developed experimental and analysis workflows to extend this technology to suboptimal input DNA conditions, including ultra-low
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Symmetry-breaking malachite green as a near-infrared light-activated fluorogenic photosensitizer for RNA proximity labeling Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-26 Lan Li, Jinghua Han, Hei-Yong G Lo, Winnie Wai Ling Tam, Han Jia, Edmund Chun Ming Tse, J Matthew Taliaferro, Ying Li
Cellular RNA is asymmetrically distributed in cells and the regulation of RNA localization is crucial for proper cellular functions. However, limited chemical tools are available to capture dynamic RNA localization in complex biological systems with high spatiotemporal resolution. Here, we developed a new method for RNA proximity labeling activated by near-infrared (NIR) light, which holds the potential
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Mechanistic insights into the alternative ribosome recycling by HflXr Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-26 Savannah M Seely, Ritwika S Basu, Matthieu G Gagnon
During stress conditions such as heat shock and antibiotic exposure, ribosomes stall on messenger RNAs, leading to inhibition of protein synthesis. To remobilize ribosomes, bacteria use rescue factors such as HflXr, a homolog of the conserved housekeeping GTPase HflX that catalyzes the dissociation of translationally inactive ribosomes into individual subunits. Here we use time-resolved cryo-electron
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Processivity and specificity of histone acetylation by the male-specific lethal complex Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-26 Anna E Kiss, Anuroop V Venkatasubramani, Dilan Pathirana, Silke Krause, Aline Campos Sparr, Jan Hasenauer, Axel Imhof, Marisa Müller, Peter B Becker
Acetylation of lysine 16 of histone H4 (H4K16ac) stands out among the histone modifications, because it decompacts the chromatin fiber. The metazoan acetyltransferase MOF (KAT8) regulates transcription through H4K16 acetylation. Antibody-based studies had yielded inconclusive results about the selectivity of MOF to acetylate the H4 N-terminus. We used targeted mass spectrometry to examine the activity
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G-quadruplex-mediated genomic instability drives SNVs in cancer Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-26 Tilmann Richl, Jochen Kuper, Caroline Kisker
G-quadruplex (G4s) DNA structures have been implicated in inducing genomic instability and contributing to cancer development. However, the relationship between G4s and cancer-related single nucleotide variants (cSNVs) in clinical settings remains unclear. In this large-scale study, we integrated experimentally validated G4s with genomic cSNVs from 13480 cancer patients to investigate the spatial association
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DNA-PK controls Apollo’s access to leading-end telomeres Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-26 Ceylan Sonmez, Beatrice Toia, Patrik Eickhoff, Andreea Medeea Matei, Michael El Beyrouthy, Björn Wallner, Max E Douglas, Titia de Lange, Francisca Lottersberger
The complex formed by Ku70/80 and DNA-PKcs (DNA-PK) promotes the synapsis and the joining of double strand breaks (DSBs) during canonical non-homologous end joining (c-NHEJ). In c-NHEJ during V(D)J recombination, DNA-PK promotes the processing of the ends and the opening of the DNA hairpins by recruiting and/or activating the nuclease Artemis/DCLRE1C/SNM1C. Paradoxically, DNA-PK is also required to
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Novel mechanisms of diversity generation in Acinetobacter baumannii resistance islands driven by Tn7-like elements Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-26 Alberto Correa, Saadlee Shehreen, Laura Chacon Machado, Jordan Thesier, Lille M Cunic, Michael T Petassi, Joshua Chu, Bennett J Kapili, Yu Jia, Kevin A England, Joseph E Peters
Mobile genetic elements play an important role in the acquisition of antibiotic and biocide resistance, especially through the formation of resistance islands in bacterial chromosomes. We analyzed the contribution of Tn7-like transposons to island formation and diversification in the nosocomial pathogen Acinetobacter baumannii and identified four separate families that recognize different integration
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Pathogenic CANVAS (AAGGG)n repeats stall DNA replication due to the formation of alternative DNA structures Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-21 Julia A Hisey, Elina A Radchenko, Nicholas H Mandel, Ryan J McGinty, Gabriel Matos-Rodrigues, Anastasia Rastokina, Chiara Masnovo, Silvia Ceschi, Alfredo Hernandez, André Nussenzweig, Sergei M Mirkin
CANVAS is a recently characterized repeat expansion disease, most commonly caused by homozygous expansions of an intronic (A2G3)n repeat in the RFC1 gene. There are a multitude of repeat motifs found in the human population at this locus, some of which are pathogenic and others benign. In this study, we conducted structure-functional analyses of the pathogenic (A2G3)n and nonpathogenic (A4G)n repeats
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Correcting 4sU induced quantification bias in nucleotide conversion RNA-seq data Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-21 Kevin Berg, Manivel Lodha, Isabel Delazer, Karolina Bartosik, Yilliam Cruz Garcia, Thomas Hennig, Elmar Wolf, Lars Dölken, Alexandra Lusser, Bhupesh K Prusty, Florian Erhard
Nucleoside analogues like 4-thiouridine (4sU) are used to metabolically label newly synthesized RNA. Chemical conversion of 4sU before sequencing induces T-to-C mismatches in reads sequenced from labelled RNA, allowing to obtain total and labelled RNA expression profiles from a single sequencing library. Cytotoxicity due to extended periods of labelling or high 4sU concentrations has been described
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The origin recognition complex requires chromatin tethering by a hypervariable intrinsically disordered region that is functionally conserved from sponge to man Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-21 Olubu A Adiji, Brendan S McConnell, Matthew W Parker
The first step toward eukaryotic genome duplication is loading of the replicative helicase onto chromatin. This ‘licensing’ step initiates with the recruitment of the origin recognition complex (ORC) to chromatin, which is thought to occur via ORC’s ATP-dependent DNA binding and encirclement activity. However, we have previously shown that ATP binding is dispensable for the chromatin recruitment of
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RNA-binding properties orchestrate TDP-43 homeostasis through condensate formation in vivo Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-21 Natalie M Scherer, Cindy Maurel, Matthew S Graus, Luke McAlary, Grant Richter, Rowan A W Radford, Alison Hogan, Emily K Don, Albert Lee, Justin Yerbury, Mathias Francois, Roger S Chung, Marco Morsch
Insoluble cytoplasmic aggregate formation of the RNA-binding protein TDP-43 is a major hallmark of neurodegenerative diseases including Amyotrophic Lateral Sclerosis. TDP-43 localizes predominantly in the nucleus, arranging itself into dynamic condensates through liquid–liquid phase separation (LLPS). Mutations and post-translational modifications can alter the condensation properties of TDP-43, contributing
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Influence of RNA circularity on Target RNA-Directed MicroRNA Degradation Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-21 Federico Fuchs Wightman, Jerónimo Lukin, Sebastián A Giusti, Michael Soutschek, Laureano Bragado, Berta Pozzi, María L Pierelli, Paula González, Juan P Fededa, Gerhard Schratt, Rina Fujiwara, Jeremy E Wilusz, Damián Refojo, Manuel de la Mata
A subset of circular RNAs (circRNAs) and linear RNAs have been proposed to ‘sponge’ or block microRNA activity. Additionally, certain RNAs induce microRNA destruction through the process of Target RNA-Directed MicroRNA Degradation (TDMD), but whether both linear and circular transcripts are equivalent in driving TDMD is unknown. Here, we studied whether circular/linear topology of endogenous and artificial
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Structure of native four-repeat satellite III sequence with non-canonical base interactions Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-21 Erin Chen, Marko Trajkovski, Hyun Kyung Lee, Samantha Nyovanie, Kailey N Martin, William L Dean, Mamta Tahiliani, Janez Plavec, Liliya A Yatsunyk
Tandem-repetitive DNA (where two or more DNA bases are repeated numerous times) can adopt non-canonical secondary structures. Many of these structures are implicated in important biological processes. Human Satellite III (HSat3) is enriched for tandem repeats of the sequence ATGGA and is located in pericentromeric heterochromatin in many human chromosomes. Here, we investigate the secondary structure
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Dynamics of miRNA accumulation during C. elegans larval development Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-21 Smita Nahar, Lucas J Morales Moya, Jana Brunner, Gert-Jan Hendriks, Benjamin Towbin, Yannick P Hauser, Giovanna Brancati, Dimos Gaidatzis, Helge Großhans
Temporally and spatially controlled accumulation underlies the functions of microRNAs (miRNAs) in various developmental processes. In Caenorhabditis elegans, this is exemplified by the temporal patterning miRNAs lin-4 and let-7, but for most miRNAs, developmental expression patterns remain poorly resolved. Indeed, experimentally observed long half-lives may constrain possible dynamics. Here, we profile
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A system of reporters for comparative investigation of EJC-independent and EJC-enhanced nonsense-mediated mRNA decay Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-20 Divya Kolakada, Amy E Campbell, Laura Baquero Galvis, Zhongyou Li, Mlana Lore, Sujatha Jagannathan
Nonsense-mediated mRNA decay (NMD) is a network of pathways that degrades transcripts that undergo premature translation termination. In mammals, NMD can be divided into the exon junction complex (EJC)-enhanced and EJC-independent branches. Fluorescence- and luminescence-based reporters have long been effective tools to investigate NMD, yet existing reporters largely focus on the EJC-enhanced pathway
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A sensitive and scalable fluorescence anisotropy single stranded RNA targeting approach for monitoring riboswitch conformational states Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-20 Maira Rivera, Omma S Ayon, Suzana Diaconescu-Grabari, Joshua Pottel, Nicolas Moitessier, Anthony Mittermaier, Maureen McKeague
The capacity of riboswitches to undergo conformational changes in response to binding their native ligands is closely tied to their functional roles and is an attractive target for antimicrobial drug design. Here, we established a probe-based fluorescence anisotropy assay to monitor riboswitch conformational switching with high sensitivity and throughput. Using the Bacillus subtillis yitJ S-Box (SAM-I)
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Landscape of RNA pseudouridylation in archaeon Sulfolobus islandicus Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-20 Yuqian Li, Songlin Wu, Keqiong Ye
Pseudouridine, one of the most abundant RNA modifications, is synthesized by stand-alone or RNA-guided pseudouridine synthases. Here, we comprehensively mapped pseudouridines in rRNAs, tRNAs and small RNAs in the archaeon Sulfolobus islandicus and identified Cbf5-associated H/ACA RNAs. Through genetic deletion and in vitro modification assays, we determined the responsible enzymes for these modifications
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The SMC5/6 complex: folding chromosomes back into shape when genomes take a break Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-20 Shamayita Roy, Hemanta Adhikary, Damien D’Amours
High-level folding of chromatin is a key determinant of the shape and functional state of chromosomes. During cell division, structural maintenance of chromosome (SMC) complexes such as condensin and cohesin ensure large-scale folding of chromatin into visible chromosomes. In contrast, the SMC5/6 complex plays more local and context-specific roles in the structural organization of interphase chromosomes
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Evolution of microRNAs in Amoebozoa and implications for the origin of multicellularity Nucleic Acids Res. (IF 14.9) Pub Date : 2024-02-20 Bart Edelbroek, Jonas Kjellin, Inna Biryukova, Zhen Liao, Torgny Lundberg, Angelika A Noegel, Ludwig Eichinger, Marc R Friedländer, Fredrik Söderbom
MicroRNAs (miRNAs) are important and ubiquitous regulators of gene expression in both plants and animals. They are thought to have evolved convergently in these lineages and hypothesized to have played a role in the evolution of multicellularity. In line with this hypothesis, miRNAs have so far only been described in few unicellular eukaryotes. Here, we investigate the presence and evolution of miRNAs