-
RNAscape: geometric mapping and customizable visualization of RNA structure Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-17 Raktim Mitra, Ari S Cohen, Remo Rohs
Analyzing and visualizing the tertiary structure and complex interactions of RNA is essential for being able to mechanistically decipher their molecular functions in vivo. Secondary structure visualization software can portray many aspects of RNA; however, these layouts are often unable to preserve topological correspondence since they do not consider tertiary interactions between different regions
-
Human AAA+ ATPase FIGNL1 suppresses RAD51-mediated ultra-fine bridge formation Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-10 Kenichiro Matsuzaki, Akira Shinohara, Miki Shinohara
RAD51 filament is crucial for the homology-dependent repair of DNA double-strand breaks and stalled DNA replication fork protection. Positive and negative regulators control RAD51 filament assembly and disassembly. RAD51 is vital for genome integrity but excessive accumulation of RAD51 on chromatin causes genome instability and growth defects. However, the detailed mechanism underlying RAD51 disassembly
-
Assembly of SARS-CoV-2 nucleocapsid protein with nucleic acid Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-08 Huaying Zhao, Abdullah M Syed, Mir M Khalid, Ai Nguyen, Alison Ciling, Di Wu, Wai-Ming Yau, Sanjana Srinivasan, Dominic Esposito, Jennifer A Doudna, Grzegorz Piszczek, Melanie Ott, Peter Schuck
The viral genome of SARS-CoV-2 is packaged by the nucleocapsid (N-)protein into ribonucleoprotein particles (RNPs), 38 ± 10 of which are contained in each virion. Their architecture has remained unclear due to the pleomorphism of RNPs, the high flexibility of N-protein intrinsically disordered regions, and highly multivalent interactions between viral RNA and N-protein binding sites in both N-terminal
-
Disruption of G-quadruplex dynamicity by BRCA2 abrogation instigates phase separation and break-induced replication at telomeres Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-08 Jennifer J Lee, Hyungmin Kim, Haemin Park, UkJin Lee, Chaelim Kim, Min Lee, Yongdae Shin, Ji-Jung Jung, Han-Byoel Lee, Wonshik Han, Hyunsook Lee
Dynamic interaction between BRCA2 and telomeric G-quadruplexes (G4) is crucial for maintaining telomere replication homeostasis. Cells lacking BRCA2 display telomeric damage with a subset of these cells bypassing senescence to initiate break-induced replication (BIR) for telomere synthesis. Here we show that the abnormal stabilization of telomeric G4 following BRCA2 depletion leads to telomeric repeat-containing
-
Identifying human pre-mRNA cleavage and polyadenylation factors by genome-wide CRISPR screens using a dual fluorescence readthrough reporter Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-08 Zuyao Ni, Nujhat Ahmed, Syed Nabeel-Shah, Xinghua Guo, Shuye Pu, Jingwen Song, Edyta Marcon, Giovanni L Burke, Amy Hin Yan Tong, Katherine Chan, Kevin C H Ha, Benjamin J Blencowe, Jason Moffat, Jack F Greenblatt
Messenger RNA precursors (pre-mRNA) generally undergo 3′ end processing by cleavage and polyadenylation (CPA), which is specified by a polyadenylation site (PAS) and adjacent RNA sequences and regulated by a large variety of core and auxiliary CPA factors. To date, most of the human CPA factors have been discovered through biochemical and proteomic studies. However, genetic identification of the human
-
Bridging DNA contacts allow Dps from E. coli to condense DNA Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-04 Sneha Shahu, Natalia Vtyurina, Moumita Das, Anne S Meyer, Mahipal Ganji, Elio A Abbondanzieri
The DNA-binding protein from starved cells (Dps) plays a crucial role in maintaining bacterial cell viability during periods of stress. Dps is a nucleoid-associated protein that interacts with DNA to create biomolecular condensates in live bacteria. Purified Dps protein can also rapidly form large complexes when combined with DNA in vitro. However, the mechanism that allows these complexes to nucleate
-
PubTator 3.0: an AI-powered literature resource for unlocking biomedical knowledge Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-04 Chih-Hsuan Wei, Alexis Allot, Po-Ting Lai, Robert Leaman, Shubo Tian, Ling Luo, Qiao Jin, Zhizheng Wang, Qingyu Chen, Zhiyong Lu
PubTator 3.0 (https://www.ncbi.nlm.nih.gov/research/pubtator3/) is a biomedical literature resource using state-of-the-art AI techniques to offer semantic and relation searches for key concepts like proteins, genetic variants, diseases and chemicals. It currently provides over one billion entity and relation annotations across approximately 36 million PubMed abstracts and 6 million full-text articles
-
Protein G-quadruplex interactions and their effects on phase transitions and protein aggregation Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-04 Bikash R Sahoo, Vojč Kocman, Nathan Clark, Nikhil Myers, Xiexiong Deng, Ee L Wong, Harry J Yang, Anita Kotar, Bryan B Guzman, Daniel Dominguez, Janez Plavec, James C A Bardwell
The SERF family of proteins were originally discovered for their ability to accelerate amyloid formation. Znf706 is an uncharacterized protein whose N-terminus is homologous to SERF proteins. We show here that human Znf706 can promote protein aggregation and amyloid formation. Unexpectedly, Znf706 specifically interacts with stable, non-canonical nucleic acid structures known as G-quadruplexes. G-quadruplexes
-
Fine-tuning the tRNA anticodon arm for multiple/consecutive incorporations of β-amino acids and analogs Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-04 Takayuki Katoh, Hiroaki Suga
Ribosomal incorporation of β-amino acids into nascent peptides is much less efficient than that of the canonical α-amino acids. To overcome this, we have engineered a tRNA chimera bearing T-stem of tRNAGlu and D-arm of tRNAPro1, referred to as tRNAPro1E2, which efficiently recruits EF-Tu and EF-P. Using tRNAPro1E2 indeed improved β-amino acid incorporation. However, multiple/consecutive incorporations
-
SingmiR: a single-cell miRNA alignment and analysis tool Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-04 Annika Engel, Shusruto Rishik, Pascal Hirsch, Verena Keller, Tobias Fehlmann, Fabian Kern, Andreas Keller
Single-cell RNA sequencing (RNA-seq) has revolutionized our understanding of cell biology, developmental and pathophysiological molecular processes, paving the way toward novel diagnostic and therapeutic approaches. However, most of the gene regulatory processes on the single-cell level are still unknown, including post-transcriptional control conferred by microRNAs (miRNAs). Like the established single-cell
-
ADMETlab 3.0: an updated comprehensive online ADMET prediction platform enhanced with broader coverage, improved performance, API functionality and decision support Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-04 Li Fu, Shaohua Shi, Jiacai Yi, Ningning Wang, Yuanhang He, Zhenxing Wu, Jinfu Peng, Youchao Deng, Wenxuan Wang, Chengkun Wu, Aiping Lyu, Xiangxiang Zeng, Wentao Zhao, Tingjun Hou, Dongsheng Cao
ADMETlab 3.0 is the second updated version of the web server that provides a comprehensive and efficient platform for evaluating ADMET-related parameters as well as physicochemical properties and medicinal chemistry characteristics involved in the drug discovery process. This new release addresses the limitations of the previous version and offers broader coverage, improved performance, API functionality
-
DEGRONOPEDIA: a web server for proteome-wide inspection of degrons Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-03 Natalia A Szulc, Filip Stefaniak, Małgorzata Piechota, Anna Soszyńska, Gabriela Piórkowska, Andrea Cappannini, Janusz M Bujnicki, Chiara Maniaci, Wojciech Pokrzywa
E3 ubiquitin ligases recognize substrates through their short linear motifs termed degrons. While degron-signaling has been a subject of extensive study, resources for its systematic screening are limited. To bridge this gap, we developed DEGRONOPEDIA, a web server that searches for degrons and maps them to nearby residues that can undergo ubiquitination and disordered regions, which may act as protein
-
The effect of pseudoknot base pairing on cotranscriptional structural switching of the fluoride riboswitch Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-03 Laura M Hertz, Elise N White, Konstantin Kuznedelov, Luyi Cheng, Angela M Yu, Rivaan Kakkaramadam, Konstantin Severinov, Alan Chen, Julius B Lucks
A central question in biology is how RNA sequence changes influence dynamic conformational changes during cotranscriptional folding. Here we investigated this question through the study of transcriptional fluoride riboswitches, non-coding RNAs that sense the fluoride anion through the coordinated folding and rearrangement of a pseudoknotted aptamer domain and a downstream intrinsic terminator expression
-
H3.1/3.2 regulate the initial progression of the gene expression program Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-03 Satoshi Funaya, Yusuke Takahashi, Masataka G Suzuki, Yutaka Suzuki, Fugaku Aoki
In mice, transcription from the zygotic genome is initiated at the mid-one-cell stage, and occurs promiscuously in many areas of the genome, including intergenic regions. Regulated transcription from selected genes is established during the two-cell stage. This dramatic change in the gene expression pattern marks the initiation of the gene expression program and is essential for early development.
-
Mitolnc controls cardiac BCAA metabolism and heart hypertrophy by allosteric activation of BCKDH Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-03 Maria Weiss, Sara Hettrich, Theresa Hofmann, Salma Hachim, Stefan Günther, Thomas Braun, Thomas Boettger
Enzyme activity is determined by various different mechanisms, including posttranslational modifications and allosteric regulation. Allosteric activators are often metabolites but other molecules serve similar functions. So far, examples of long non-coding RNAs (lncRNAs) acting as allosteric activators of enzyme activity are missing. Here, we describe the function of mitolnc in cardiomyocytes, a nuclear
-
Resolving the intricate binding of neomycin B to multiple binding motifs of a neomycin-sensing riboswitch aptamer by native top-down mass spectrometry and NMR spectroscopy Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-03 Sarah Viola Heel, Fabian Juen, Karolina Bartosik, Ronald Micura, Christoph Kreutz, Kathrin Breuker
Understanding small molecule binding to RNA can be complicated by an intricate interplay between binding stoichiometry, multiple binding motifs, different occupancies of different binding motifs, and changes in the structure of the RNA under study. Here, we use native top-down mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy to experimentally resolve these factors and gain a
-
RecA-dependent or independent recombination of plasmid DNA generates a conflict with the host EcoKI immunity by launching restriction alleviation Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-03 Mikhail Skutel, Daria Yanovskaya, Alina Demkina, Aleksandr Shenfeld, Olga Musharova, Konstantin Severinov, Artem Isaev
Bacterial defence systems are tightly regulated to avoid autoimmunity. In Type I restriction–modification (R–M) systems, a specific mechanism called restriction alleviation (RA) controls the activity of the restriction module. In the case of the Escherichia coli Type I R–M system EcoKI, RA proceeds through ClpXP-mediated proteolysis of restriction complexes bound to non-methylated sites that appear
-
BRD2 promotes antibody class switch recombination by facilitating DNA repair in collaboration with NIPBL Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-03 Santosh K Gothwal, Ahmed M Refaat, Mikiyo Nakata, Andre Stanlie, Tasuku Honjo, Nasim A Begum
Efficient repair of DNA double-strand breaks in the Ig heavy chain gene locus is crucial for B-cell antibody class switch recombination (CSR). The regulatory dynamics of the repair pathway direct CSR preferentially through nonhomologous end joining (NHEJ) over alternative end joining (AEJ). Here, we demonstrate that the histone acetyl reader BRD2 suppresses AEJ and aberrant recombination as well as
-
Multiplexed in-situ mutagenesis driven by a dCas12a-based dual-function base editor Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-03 Yaokang Wu, Yang Li, Yanfeng Liu, Xiang Xiu, Jiaheng Liu, Linpei Zhang, Jianghua Li, Guocheng Du, Xueqin Lv, Jian Chen, Rodrigo Ledesma-Amaro, Long Liu
Mutagenesis driving genetic diversity is vital for understanding and engineering biological systems. However, the lack of effective methods to generate in-situ mutagenesis in multiple genomic loci combinatorially limits the study of complex biological functions. Here, we design and construct MultiduBE, a dCas12a-based multiplexed dual-function base editor, in an all-in-one plasmid for performing combinatorial
-
Unearthing a novel function of SRSF1 in binding and unfolding of RNA G-quadruplexes Nucleic Acids Res. (IF 14.9) Pub Date : 2024-04-03 Naiduwadura Ivon Upekala De Silva, Nathan Lehman, Talia Fargason, Trenton Paul, Zihan Zhang, Jun Zhang
SRSF1 governs splicing of over 1500 mRNA transcripts. SRSF1 contains two RNA-recognition motifs (RRMs) and a C-terminal Arg/Ser-rich region (RS). It has been thought that SRSF1 RRMs exclusively recognize single-stranded exonic splicing enhancers, while RS lacks RNA-binding specificity. With our success in solving the insolubility problem of SRSF1, we can explore the unknown RNA-binding landscape of
-
A phage nucleus-associated RNA-binding protein is required for jumbo phage infection Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-30 Eray Enustun, Emily G Armbruster, Jina Lee, Sitao Zhang, Brian A Yee, Kseniya Malukhina, Yajie Gu, Amar Deep, Jack T Naritomi, Qishan Liang, Stefan Aigner, Benjamin A Adler, Brady F Cress, Jennifer A Doudna, Vorrapon Chaikeeratisak, Don W Cleveland, Majid Ghassemian, Bogdan Bintu, Gene W Yeo, Joe Pogliano, Kevin D Corbett
Large-genome bacteriophages (jumbo phages) of the proposed family Chimalliviridae assemble a nucleus-like compartment bounded by a protein shell that protects the replicating phage genome from host-encoded restriction enzymes and DNA-targeting CRISPR-Cas nucleases. While the nuclear shell provides broad protection against host nucleases, it necessitates transport of mRNA out of the nucleus-like compartment
-
Critical steps in the assembly process of the bacterial 50S ribosomal subunit Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-30 Amal Seffouh, Rainer Nikolay, Joaquin Ortega
During assembly, ribosomal particles in bacteria fold according to energy landscapes comprised of multiple parallel pathways. Cryo-electron microscopy studies have identified a critical maturation step that occurs during the late assembly stages of the 50S subunit in Bacillus subtilis. This step acts as a point of convergency for all the parallel assembly pathways of the subunit, where an assembly
-
APLF facilitates interstrand DNA crosslink repair and replication fork protection to confer cisplatin resistance Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-23 Cheng-Kuei Wu, Jia-Lin Shiu, Chao-Liang Wu, Chi-Feng Hung, Yen-Chih Ho, Yen-Tzu Chen, Sheng-Yung Tung, Cheng-Fa Yeh, Che-Hung Shen, Hungjiun Liaw, Wen-Pin Su
Replication stress converts the stalled forks into reversed forks, which is an important protection mechanism to prevent fork degradation and collapse into poisonous DNA double-strand breaks (DSBs). Paradoxically, the mechanism also acts in cancer cells to contribute to chemoresistance against various DNA-damaging agents. PARP1 binds to and is activated by stalled forks to facilitate fork reversal
-
S-phase checkpoint prevents leading strand degradation from strand-associated nicks at stalled replication forks Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-23 Alberto Bugallo, Mar Sánchez, María Fernández-García, Mónica Segurado
The S-phase checkpoint is involved in coupling DNA unwinding with nascent strand synthesis and is critical to maintain replication fork stability in conditions of replicative stress. However, its role in the specific regulation of leading and lagging strands at stalled forks is unclear. By conditionally depleting RNaseH2 and analyzing polymerase usage genome-wide, we examine the enzymology of DNA replication
-
MIWI N-terminal arginines orchestrate generation of functional pachytene piRNAs and spermiogenesis Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-23 Nicholas Vrettos, Jan Oppelt, Ansgar Zoch, Paraskevi Sgourdou, Haruka Yoshida, Brian Song, Ryan Fink, Dónal O’Carroll, Zissimos Mourelatos
N-terminal arginine (NTR) methylation is a conserved feature of PIWI proteins, which are central components of the PIWI-interacting RNA (piRNA) pathway. The significance and precise function of PIWI NTR methylation in mammals remains unknown. In mice, PIWI NTRs bind Tudor domain containing proteins (TDRDs) that have essential roles in piRNA biogenesis and the formation of the chromatoid body. Using
-
The zinc-finger protein Z4 cooperates with condensin II to regulate somatic chromosome pairing and 3D chromatin organization Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-23 Marta Puerto, Mamta Shukla, Paula Bujosa, Juan Pérez-Roldán, Mònica Torràs-Llort, Srividya Tamirisa, Albert Carbonell, Carme Solé, Joynob Akter Puspo, Christopher T Cummings, Eulàlia de Nadal, Francesc Posas, Fernando Azorín, M Jordan Rowley
Chromosome pairing constitutes an important level of genome organization, yet the mechanisms that regulate pairing in somatic cells and the impact on 3D chromatin organization are still poorly understood. Here, we address these questions in Drosophila, an organism with robust somatic pairing. In Drosophila, pairing preferentially occurs at loci consisting of numerous architectural protein binding sites
-
ARGLU1 enhances promoter-proximal pausing of RNA polymerase II and stimulates DNA damage repair Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-23 Scott Bachus, Nikolas Akkerman, Lauren Fulham, Drayson Graves, Rafe Helwer, Jordan Rempel, Peter Pelka
Arginine and glutamate rich 1 (ARGLU1) is a poorly understood cellular protein with functions in RNA splicing and transcription. Computational prediction suggests that ARGLU1 contains intrinsically disordered regions and lacks any known structural or functional domains. We used adenovirus Early protein 1A (E1A) to probe for critical regulators of important cellular pathways and identified ARGLU1 as
-
txtools: an R package facilitating analysis of RNA modifications, structures, and interactions Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-21 Miguel Angel Garcia-Campos, Schraga Schwartz
We present txtools, an R package that enables the processing, analysis, and visualization of RNA-seq data at the nucleotide-level resolution, seamlessly integrating alignments to the genome with transcriptomic representation. txtools’ main inputs are BAM files and a transcriptome annotation, and the main output is a table, capturing mismatches, deletions, and the number of reads beginning and ending
-
Dux activates metabolism-lactylation-MET network during early iPSC reprogramming with Brg1 as the histone lactylation reader Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-21 Xinglin Hu, Xingwei Huang, Yue Yang, Yuchen Sun, Yanhua Zhao, Zhijing Zhang, Dan Qiu, Yanshuang Wu, Guangming Wu, Lei Lei
The process of induced pluripotent stem cells (iPSCs) reprogramming involves several crucial events, including the mesenchymal-epithelial transition (MET), activation of pluripotent genes, metabolic reprogramming, and epigenetic rewiring. Although these events intricately interact and influence each other, the specific element that regulates the reprogramming network remains unclear. Dux, a factor
-
Comprehensive analysis of intramolecular G-quadruplex structures: furthering the understanding of their formalism Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-21 Marc Farag, Liliane Mouawad
G-quadruplexes (G4) are helical structures found in guanine-rich DNA or RNA sequences. Generally, their formalism is based on a few dozen structures, which can produce some inconsistencies or incompleteness. Using the website ASC-G4, we analyzed the structures of 333 intramolecular G4s, of all types, which allowed us to clarify some key concepts and present new information. To each of the eight distinguishable
-
FUS reads histone H3K36me3 to regulate alternative polyadenylation Nucleic Acids Res. (IF 14.9) Pub Date : 2024-03-19 Junqi Jia, Haonan Fan, Xinyi Wan, Yuan Fang, Zhuoning Li, Yin Tang, Yanjun Zhang, Jun Huang, Dong Fang
Complex organisms generate differential gene expression through the same set of DNA sequences in distinct cells. The communication between chromatin and RNA regulates cellular behavior in tissues. However, little is known about how chromatin, especially histone modifications, regulates RNA polyadenylation. In this study, we found that FUS was recruited to chromatin by H3K36me3 at gene bodies. The H3K36me3
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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)
-
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
-
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
-
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
-
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
-
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