-
Differential roles of positive and negative supercoiling in organizing the E. coli genome Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-05 Ziqi Fu, Monica S Guo, Weiqiang Zhou, Jie Xiao
This study aims to explore whether and how positive and negative supercoiling contribute to the three-dimensional (3D) organization of the bacterial genome. We used recently published Escherichia coli GapR ChIP-seq and TopoI ChIP-seq (also called EcTopoI-seq) data, which marks positive and negative supercoiling sites, respectively, to study how supercoiling correlates with the spatial contact maps
-
Contribution of tRNA sequence and modifications to the decoding preferences of E. coli and M. mycoides tRNAGlyUCC for synonymous glycine codons Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-05 Maria Kompatscher, Karolina Bartosik, Kevin Erharter, Raphael Plangger, Fabian Sebastian Juen, Christoph Kreutz, Ronald Micura, Eric Westhof, Matthias D Erlacher
tRNA superwobbling, used by certain bacteria and organelles, is an intriguing decoding concept in which a single tRNA isoacceptor is used to decode all synonymous codons of a four-fold degenerate codon box. While Escherichia coli relies on three tRNAGly isoacceptors to decode the four glycine codons (GGN), Mycoplasma mycoides requires only a single tRNAGly. Both organisms express tRNAGly with the anticodon
-
Alternative cleavage and polyadenylation of the Ccnb1 mRNA defines accumulation of cyclin protein during the meiotic cell cycle Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-04 Xiaotian Wang, Fang-Shiuan Leung, Jeffrey O Bush, Marco Conti
Progression through the mitotic and meiotic cell cycle is driven by fluctuations in the levels of cyclins, the regulatory subunits controlling the localization and activity of CDK1 kinases. Cyclin levels are regulated through a precise balance of synthesis and degradation. Here we demonstrate that the synthesis of Cyclin B1 during the oocyte meiotic cell cycle is defined by the selective translation
-
A tailed mirtron promotes longevity in Drosophila Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-04 Sweta Khanal, Matthew de Cruz, Britton Strickland, Kody Mansfield, Eric C Lai, Alex Flynt
Thousands of atypical microRNAs (miRNAs) have been described in the genomes of animals; however, it is unclear if many of these non-canonical miRNAs can measurably influence phenotypes. Mirtrons are the largest class of non-canonical miRNAs that are produced from hairpins excised by splicing, which after debranching become substrates for Dicer and load into RISC. Most mirtrons require additional processing
-
The nuclease-associated short prokaryotic Argonaute system nonspecifically degrades DNA upon activation by target recognition Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-04 Xueling Lu, Jun Xiao, Longfei Wang, Bin Zhu, Fengtao Huang
Prokaryotic Argonautes (pAgos) play a vital role in host defense by utilizing short nucleic acid guides to recognize and target complementary nucleic acids. Despite being the majority of pAgos, short pAgos have only recently received attention. Short pAgos are often associated with proteins containing an APAZ domain and a nuclease domain including DUF4365, SMEK, or HNH domain. In contrast to long pAgos
-
Post-transcriptional regulation shapes the transcriptome of quiescent budding yeast Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-04 Alison C Greenlaw, Kris G Alavattam, Toshio Tsukiyama
To facilitate long-term survival, cells must exit the cell cycle and enter quiescence, a reversible non-replicative state. Budding yeast cells reprogram their gene expression during quiescence entry to silence transcription, but how the nascent transcriptome changes in quiescence is unknown. By investigating the nascent transcriptome, we identified over a thousand noncoding RNAs in quiescent and G1
-
Dynamic action of an intrinsically disordered protein in DNA compaction that induces mycobacterial dormancy Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-04 Akihito Nishiyama, Masahiro Shimizu, Tomoyuki Narita, Noriyuki Kodera, Yuriko Ozeki, Akira Yokoyama, Kouta Mayanagi, Takehiro Yamaguchi, Mariko Hakamata, Amina Kaboso Shaban, Yoshitaka Tateishi, Kosuke Ito, Sohkichi Matsumoto
Mycobacteria are the major human pathogens with the capacity to become dormant persisters. Mycobacterial DNA-binding protein 1 (MDP1), an abundant histone-like protein in dormant mycobacteria, induces dormancy phenotypes, e.g. chromosome compaction and growth suppression. For these functions, the polycationic intrinsically disordered region (IDR) is essential. However, the disordered property of IDR
-
Enzymic recognition of amino acids drove the evolution of primordial genetic codes Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-04 Jordan Douglas, Remco Bouckaert, Charles W Carter, Peter R Wills
How genetic information gained its exquisite control over chemical processes needed to build living cells remains an enigma. Today, the aminoacyl-tRNA synthetases (AARS) execute the genetic codes in all living systems. But how did the AARS that emerged over three billion years ago as low-specificity, protozymic forms then spawn the full range of highly-specific enzymes that distinguish between 22 diverse
-
The YAP1/TAZ-TEAD transcriptional network regulates gene expression at neuromuscular junctions in skeletal muscle fibers Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-04 Lea Gessler, Danyil Huraskin, Yongzhi Jian, Nane Eiber, Zhaoyong Hu, Tomasz J Prószyński, Said Hashemolhosseini
We examined YAP1/TAZ-TEAD signaling pathway activity at neuromuscular junctions (NMJs) of skeletal muscle fibers in adult mice. Our investigations revealed that muscle-specific knockouts of Yap1 or Taz, or both, demonstrate that these transcriptional coactivators regulate synaptic gene expression, the number and morphology of NMJs, and synaptic nuclei. Yap1 or Taz single knockout mice display reduced
-
HybridDBRpred: improved sequence-based prediction of DNA-binding amino acids using annotations from structured complexes and disordered proteins Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-04 Jian Zhang, Sushmita Basu, Lukasz Kurgan
Current predictors of DNA-binding residues (DBRs) from protein sequences belong to two distinct groups, those trained on binding annotations extracted from structured protein-DNA complexes (structure-trained) vs. intrinsically disordered proteins (disorder-trained). We complete the first empirical analysis of predictive performance across the structure- and disorder-annotated proteins for a representative
-
The genetic landscape of origins of replication in P. falciparum. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-01 Casilda Muñoz Castellano,Laurent Lacroix,Emilie Mathis,Paulina Prorok,Magali Hennion,Jose-Juan Lopez-Rubio,Marcel Méchali,Ana Rita Gomes
Various origin mapping approaches have enabled genome-wide identification of origins of replication (ORI) in model organisms, but only a few studies have focused on divergent organisms. By employing three complementary approaches we provide a high-resolution map of ORIs in Plasmodium falciparum, the deadliest human malaria parasite. We profiled the distribution of origin of recognition complex (ORC)
-
MutSβ protects common fragile sites by facilitating homology-directed repair at DNA double-strand breaks with secondary structures. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-01 Youhang Li,Yunkun Zhang,Sameer Bikram Shah,Chia-Yu Chang,Hailong Wang,Xiaohua Wu
Common fragile sites (CFSs) are regions prone to chromosomal rearrangements, thereby contributing to tumorigenesis. Under replication stress (RS), CFSs often harbor under-replicated DNA regions at the onset of mitosis, triggering homology-directed repair known as mitotic DNA synthesis (MiDAS) to complete DNA replication. In this study, we identified an important role of DNA mismatch repair protein
-
Functional analysis of the AUG initiator codon context reveals novel conserved sequences that disfavor mRNA translation in eukaryotes. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-01 Greco Hernández,Alejandra García,Shira Weingarten-Gabbay,Rishi Kumar Mishra,Tanweer Hussain,Mehdi Amiri,Gabriel Moreno-Hagelsieb,Angélica Montiel-Dávalos,Paul Lasko,Nahum Sonenberg
mRNA translation is a fundamental process for life. Selection of the translation initiation site (TIS) is crucial, as it establishes the correct open reading frame for mRNA decoding. Studies in vertebrate mRNAs discovered that a purine at -3 and a G at +4 (where A of the AUG initiator codon is numbered + 1), promote TIS recognition. However, the TIS context in other eukaryotes has been poorly experimentally
-
DAXX promotes centromeric stability independently of ATRX by preventing the accumulation of R-loop-induced DNA double-stranded breaks. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-01 Lia M Pinto,Alexandros Pailas,Max Bondarchenko,Abhishek Bharadwaj Sharma,Katrin Neumann,Anthony J Rizzo,Céline Jeanty,Nathalie Nicot,Carine Racca,Mindy K Graham,Catherine Naughton,Yaqun Liu,Chun-Long Chen,Paul J Meakin,Nick Gilbert,Sébastien Britton,Alan K Meeker,Christopher M Heaphy,Florence Larminat,Eric Van Dyck
Maintaining chromatin integrity at the repetitive non-coding DNA sequences underlying centromeres is crucial to prevent replicative stress, DNA breaks and genomic instability. The concerted action of transcriptional repressors, chromatin remodelling complexes and epigenetic factors controls transcription and chromatin structure in these regions. The histone chaperone complex ATRX/DAXX is involved in
-
MAE-seq refines regulatory elements across the genome. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-01 Xiusheng Zhu,Qitong Huang,Lei Huang,Jing Luo,Qing Li,Dashuai Kong,Biao Deng,Yi Gu,Xueyan Wang,Chenying Li,Siyuan Kong,Yubo Zhang
Proper cell fate determination relies on precise spatial and temporal genome-wide cooperation between regulatory elements (REs) and their targeted genes. However, the lengths of REs defined using different methods vary, which indicates that there is sequence redundancy and that the context of the genome may be unintelligible. We developed a method called MAE-seq (Massive Active Enhancers by Sequencing)
-
Interaction of histone H4 with Cse4 facilitates conformational changes in Cse4 for its sumoylation and mislocalization. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-12-01 Kentaro Ohkuni,Wei-Chun Au,Amira Z Kazi,Mark Villamil,Peter Kaiser,Munira A Basrai
Mislocalization of overexpressed CENP-A (Cse4 in budding yeast, Cnp1 in fission yeast, CID in flies) contributes to chromosomal instability (CIN) in yeasts, flies, and human cells. Mislocalization of CENP-A is observed in many cancers and this correlates with poor prognosis. Structural mechanisms that contribute to mislocalization of CENP-A are poorly defined. Here, we show that interaction of histone
-
Editorial: Nucleic Acids Research virtual issue dedicated to nucleic acid therapeutics, 2018-2023. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-30 Jillian Belgrad,Hassan H Fakih,Krystal C Johnson,David R Corey
-
Correction to 'The P10K database: a data portal for the protist 10 000 genomes project'. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-30
-
Self-delivering, chemically modified CRISPR RNAs for AAV co-delivery and genome editing in vivo Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-30 Han Zhang, Karen Kelly, Jonathan Lee, Dimas Echeverria, David Cooper, Rebecca Panwala, Nadia Amrani, Zexiang Chen, Nicholas Gaston, Atish Wagh, Gregory A Newby, Jun Xie, David R Liu, Guangping Gao, Scot A Wolfe, Anastasia Khvorova, Jonathan K Watts, Erik J Sontheimer
Guide RNAs offer programmability for CRISPR-Cas9 genome editing but also add challenges for delivery. Chemical modification, which has been key to the success of oligonucleotide therapeutics, can enhance the stability, distribution, cellular uptake, and safety of nucleic acids. Previously, we engineered heavily and fully modified SpyCas9 crRNA and tracrRNA, which showed enhanced stability and retained
-
New design strategies for ultra-specific CRISPR-Cas13a-based RNA detection with single-nucleotide mismatch sensitivity Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-30 Adrian M Molina Vargas, Souvik Sinha, Raven Osborn, Pablo R Arantes, Amun Patel, Stephen Dewhurst, Dwight J Hardy, Andrew Cameron, Giulia Palermo, Mitchell R O’Connell
An increasingly pressing need for clinical diagnostics has required the development of novel nucleic acid-based detection technologies that are sensitive, fast, and inexpensive, and that can be deployed at point-of-care. Recently, the RNA-guided ribonuclease CRISPR-Cas13 has been successfully harnessed for such purposes. However, developing assays for detection of genetic variability, for example single-nucleotide
-
The miRNA–target interactions: An underestimated intricacy Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-30 Caroline Diener, Andreas Keller, Eckart Meese
MicroRNAs (miRNAs) play indispensable roles in posttranscriptional gene regulation. Their cellular regulatory impact is determined not solely by their sheer number, which likely amounts to >2000 individual miRNAs in human, than by the regulatory effectiveness of single miRNAs. Although, one begins to develop an understanding of the complex mechanisms underlying miRNA–target interactions (MTIs), the
-
Substrate selectivity and catalytic activation of the type III CRISPR ancillary nuclease Can2 Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-30 Kenny Jungfer, Annina Sigg, Martin Jinek
Type III CRISPR-Cas systems provide adaptive immunity against foreign mobile genetic elements through RNA-guided interference. Sequence-specific recognition of RNA targets by the type III effector complex triggers the generation of cyclic oligoadenylate (cOA) second messengers that activate ancillary effector proteins, thus reinforcing the host immune response. The ancillary nuclease Can2 is activated
-
Unveiling the RNA-mediated allosteric activation discloses functional hotspots in CRISPR-Cas13a Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-30 Souvik Sinha, Adrian M Molina Vargas, Pablo R Arantes, Amun Patel, Mitchell R O’Connell, Giulia Palermo
Cas13a is a recent addition to the CRISPR-Cas toolkit that exclusively targets RNA, which makes it a promising tool for RNA detection. It utilizes a CRISPR RNA (crRNA) to target RNA sequences and trigger a composite active site formed by two ‘Higher Eukaryotes and Prokaryotes Nucleotide’ (HEPN) domains, cleaving any solvent-exposed RNA. In this system, an intriguing form of allosteric communication
-
The 2024 Nucleic Acids Research database issue and the online molecular biology database collection Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-30 Daniel J Rigden, Xosé M Fernández
The 2024 Nucleic Acids Research database issue contains 180 papers from across biology and neighbouring disciplines. There are 90 papers reporting on new databases and 83 updates from resources previously published in the Issue. Updates from databases most recently published elsewhere account for a further seven. Nucleic acid databases include the new NAKB for structural information and updates from
-
Differentiable partition function calculation for RNA Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-28 Marco C Matthies, Ryan Krueger, Andrew E Torda, Max Ward
Ribonucleic acid (RNA) is an essential molecule in a wide range of biological functions. In 1990, McCaskill introduced a dynamic programming algorithm for computing the partition function of an RNA sequence. McCaskill’s algorithm is widely used today for understanding the thermodynamic properties of RNA. In this work, we introduce a generalization of McCaskill’s algorithm that is well-defined over
-
EMBL’s European Bioinformatics Institute (EMBL-EBI) in 2023 Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-28 Matthew Thakur, Annalisa Buniello, Catherine Brooksbank, Kim T Gurwitz, Matthew Hall, Matthew Hartley, David G Hulcoop, Andrew R Leach, Diana Marques, Maria Martin, Aziz Mithani, Ellen M McDonagh, Euphemia Mutasa-Gottgens, David Ochoa, Yasset Perez-Riverol, James Stephenson, Mihaly Varadi, Sameer Velankar, Juan Antonio Vizcaino, Rick Witham, Johanna McEntyre
The European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI) is one of the world's leading sources of public biomolecular data. Based at the Wellcome Genome Campus in Hinxton, UK, EMBL-EBI is one of six sites of the European Molecular Biology Laboratory (EMBL), Europe's only intergovernmental life sciences organisation. This overview summarises the latest developments in
-
CRISPR–dCas13a system for programmable small RNAs and polycistronic mRNA repression in bacteria Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-28 Sung Cheon Ko, Han Min Woo
Bacterial small RNAs (sRNAs) function in post-transcriptional regulatory responses to environmental changes. However, the lack of eukaryotic RNA interference-like machinery in bacteria has limited the systematic engineering of RNA repression. Here, we report the development of clustered regularly interspaced short palindromic repeats (CRISPR)-guided dead CRIPSR-associated protein 13a (dCas13a) ribonucleoprotein
-
MODOMICS: a database of RNA modifications and related information. 2023 update Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-28 Andrea Cappannini, Angana Ray, Elżbieta Purta, Sunandan Mukherjee, Pietro Boccaletto, S Naeim Moafinejad, Antony Lechner, Charles Barchet, Bruno P Klaholz, Filip Stefaniak, Janusz M Bujnicki
The MODOMICS database was updated with recent data and now includes new data types related to RNA modifications. Changes to the database include an expanded modification catalog, encompassing both natural and synthetic residues identified in RNA structures. This addition aids in representing RNA sequences from the RCSB PDB database more effectively. To manage the increased number of modifications,
-
Hi-BDiSCO: folding 3D mesoscale genome structures from Hi-C data using brownian dynamics Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-28 Zilong Li, Tamar Schlick
The structure and dynamics of the eukaryotic genome are intimately linked to gene regulation and transcriptional activity. Many chromosome conformation capture experiments like Hi-C have been developed to detect genome-wide contact frequencies and quantify loop/compartment structures for different cellular contexts and time-dependent processes. However, a full understanding of these events requires
-
ESRP1 controls biogenesis and function of a large abundant multiexon circRNA Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-28 Dawei Liu, B Kate Dredge, Andrew G Bert, Katherine A Pillman, John Toubia, Wenting Guo, Boris J A Dyakov, Melodie M Migault, Vanessa M Conn, Simon J Conn, Philip A Gregory, Anne-Claude Gingras, Dinshaw Patel, Baixing Wu, Gregory J Goodall
While the majority of circRNAs are formed from infrequent back-splicing of exons from protein coding genes, some can be produced at quite high level and in a regulated manner. We describe the regulation, biogenesis and function of circDOCK1(2–27), a large, abundant circular RNA that is highly regulated during epithelial-mesenchymal transition (EMT) and whose formation depends on the epithelial splicing
-
Interrogating two extensively self-targeting Type I CRISPR-Cas systems in Xanthomonas albilineans reveals distinct anti-CRISPR proteins that block DNA degradation Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-28 Franziska Wimmer, Frank Englert, Katharina G Wandera, Omer S Alkhnbashi, Scott P Collins, Rolf Backofen, Chase L Beisel
CRISPR-Cas systems store fragments of invader DNA as spacers to recognize and clear those same invaders in the future. Spacers can also be acquired from the host's genomic DNA, leading to lethal self-targeting. While self-targeting can be circumvented through different mechanisms, natural examples remain poorly explored. Here, we investigate extensive self-targeting by two CRISPR-Cas systems encoding
-
Chromatin accessibility and pioneer factor FOXA1 restrict glucocorticoid receptor action in prostate cancer Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-28 Laura Helminen, Jasmin Huttunen, Melina Tulonen, Niina Aaltonen, Einari A Niskanen, Jorma J Palvimo, Ville Paakinaho
Treatment of prostate cancer relies predominantly on the inhibition of androgen receptor (AR) signaling. Despite the initial effectiveness of the antiandrogen therapies, the cancer often develops resistance to the AR blockade. One mechanism of the resistance is glucocorticoid receptor (GR)-mediated replacement of AR function. Nevertheless, the mechanistic ways and means how the GR-mediated antiandrogen
-
Internal RNA 2′-O-methylation on the HIV-1 genome impairs reverse transcription Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-28 Alice Decombe, Olve Peersen, Priscila Sutto-Ortiz, Célia Chamontin, Géraldine Piorkowski, Bruno Canard, Sébastien Nisole, Etienne Decroly
Viral RNA genomes are modified by epitranscriptomic marks, including 2′-O-methylation that is added by cellular or viral methyltransferases. 2′-O-Methylation modulates RNA structure, function and discrimination between self- and non-self-RNA by innate immune sensors such as RIG-I-like receptors. This is illustrated by human immunodeficiency virus type-1 (HIV-1) that decorates its RNA genome through
-
Unraveling blunt-end RNA binding and ATPase-driven translocation activities of the RIG-I family helicase LGP2 Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-28 Kuan-Ying Lee, Candice Craig, Smita S Patel
The RIG-I family helicases, comprising RIG-I, MDA5 and LGP2, are cytoplasmic RNA sensors that trigger an antiviral immune response by specifically recognizing foreign RNAs. While LGP2 lacks the signaling domain necessary for immune activation, it plays a vital role in regulating the RIG-I/MDA5 signaling pathway. In this study, we investigate the mechanisms underlying this regulation by examining the
-
Exome-wide benchmark of difficult-to-sequence regions using short-read next-generation DNA sequencing Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-28 Atsushi Hijikata, Mikita Suyama, Shingo Kikugawa, Ryo Matoba, Takuya Naruto, Yumi Enomoto, Kenji Kurosawa, Naoki Harada, Kumiko Yanagi, Tadashi Kaname, Keisuke Miyako, Masaki Takazawa, Hideo Sasai, Junichi Hosokawa, Sakae Itoga, Tomomi Yamaguchi, Tomoki Kosho, Keiko Matsubara, Yoko Kuroki, Maki Fukami, Kaori Adachi, Eiji Nanba, Naomi Tsuchida, Yuri Uchiyama, Naomichi Matsumoto, Kunihiro Nishimura,
Next-generation DNA sequencing (NGS) in short-read mode has recently been used for genetic testing in various clinical settings. NGS data accuracy is crucial in clinical settings, and several reports regarding quality control of NGS data, primarily focusing on establishing NGS sequence read accuracy, have been published thus far. Variant calling is another critical source of NGS errors that remains
-
Correction to 'Four additional natural 7-deazaguanine derivatives in phages and how to make them'. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-27
-
Co-transcriptional folding of the glmS ribozyme enables a rapid response to metabolite Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-25 Yuan Lou, Sarah A Woodson
The glmS ribozyme riboswitch, located in the 5′ untranslated region of the Bacillus subtilis glmS messenger RNA (mRNA), regulates cell wall biosynthesis through ligand-induced self-cleavage and decay of the glmS mRNA. Although self-cleavage of the refolded glmS ribozyme has been studied extensively, it is not known how early the ribozyme folds and self-cleaves during transcription. Here, we combine
-
CropGS-Hub: a comprehensive database of genotype and phenotype resources for genomic prediction in major crops Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-25 Jiaxin Chen, Cong Tan, Min Zhu, Chenyang Zhang, Zhihan Wang, Xuemei Ni, Yanlin Liu, Tong Wei, XiaoFeng Wei, Xiaodong Fang, Yang Xu, Xuehui Huang, Jie Qiu, Huan Liu
The explosive amount of multi-omics data has brought a paradigm shift both in academic research and further application in life science. However, managing and reusing the growing resources of genomic and phenotype data points presents considerable challenges for the research community. There is an urgent need for an integrated database that combines genome-wide association studies (GWAS) with genomic
-
Supercoiling-dependent DNA binding: quantitative modeling and applications to bulk and single-molecule experiments Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-25 Pauline J Kolbeck, Miloš Tišma, Brian T Analikwu, Willem Vanderlinden, Cees Dekker, Jan Lipfert
DNA stores our genetic information and is ubiquitous in applications, where it interacts with binding partners ranging from small molecules to large macromolecular complexes. Binding is modulated by mechanical strains in the molecule and can change local DNA structure. Frequently, DNA occurs in closed topological forms where topology and supercoiling add a global constraint to the interplay of binding-induced
-
RNA-binding protein Nocte regulates Drosophila development by promoting translation reinitiation on mRNAs with long upstream open reading frames Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-25 Tianyi Zhang, Yutong Xue, Shuaikun Su, Valerie Altouma, Katherine Ho, Jennifer L Martindale, Seung-Kyu Lee, Weiping Shen, Aaron Park, Yongqing Zhang, Supriyo De, Myriam Gorospe, Weidong Wang
RNA-binding proteins (RBPs) with intrinsically disordered regions (IDRs) are linked to multiple human disorders, but their mechanisms of action remain unclear. Here, we report that one such protein, Nocte, is essential for Drosophila eye development by regulating a critical gene expression cascade at translational level. Knockout of nocte in flies leads to lethality, and its eye-specific depletion
-
The SysteMHC Atlas v2.0, an updated resource for mass spectrometry-based immunopeptidomics. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-24 Xiaoxiang Huang,Ziao Gan,Haowei Cui,Tian Lan,Yansheng Liu,Etienne Caron,Wenguang Shao
The SysteMHC Atlas v1.0 was the first public repository dedicated to mass spectrometry-based immunopeptidomics. Here we introduce a newly released version of the SysteMHC Atlas v2.0 (https://systemhc.sjtu.edu.cn), a comprehensive collection of 7190 MS files from 303 allotypes. We extended and optimized a computational pipeline that allows the identification of MHC-bound peptides carrying on unexpected
-
RPA guides UNG to uracil in ssDNA to facilitate antibody class switching and repair of mutagenic uracil at the replication fork. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-24 Abdul B Hayran,Nina B Liabakk,Per A Aas,Anna Kusnierczyk,Cathrine B Vågbø,Antonio Sarno,Tobias S Iveland,Konika Chawla,Astrid Zahn,Javier M Di Noia,Geir Slupphaug,Bodil Kavli
Activation-induced cytidine deaminase (AID) interacts with replication protein A (RPA), the major ssDNA-binding protein, to promote deamination of cytosine to uracil in transcribed immunoglobulin (Ig) genes. Uracil-DNA glycosylase (UNG) acts in concert with AID during Ig diversification. In addition, UNG preserves genome integrity by base-excision repair (BER) in the overall genome. How UNG is regulated
-
GproteinDb in 2024: new G protein-GPCR couplings, AlphaFold2-multimer models and interface interactions. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-24 Gáspár Pándy-Szekeres,Luis P Taracena Herrera,Jimmy Caroli,Ali A Kermani,Yashraj Kulkarni,György M Keserű,David E Gloriam
G proteins are the major signal proteins of ∼800 receptors for medicines, hormones, neurotransmitters, tastants and odorants. GproteinDb offers integrated genomic, structural, and pharmacological data and tools for analysis, visualization and experiment design. Here, we present the first major update of GproteinDb greatly expanding its coupling data and structural templates, adding AlphaFold2 structure
-
The Monarch Initiative in 2024: an analytic platform integrating phenotypes, genes and diseases across species. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-24 Tim E Putman,Kevin Schaper,Nicolas Matentzoglu,Vincent P Rubinetti,Faisal S Alquaddoomi,Corey Cox,J Harry Caufield,Glass Elsarboukh,Sarah Gehrke,Harshad Hegde,Justin T Reese,Ian Braun,Richard M Bruskiewich,Luca Cappelletti,Seth Carbon,Anita R Caron,Lauren E Chan,Christopher G Chute,Katherina G Cortes,Vinícius De Souza,Tommaso Fontana,Nomi L Harris,Emily L Hartley,Eric Hurwitz,Julius O B Jacobsen,Madan
Bridging the gap between genetic variations, environmental determinants, and phenotypic outcomes is critical for supporting clinical diagnosis and understanding mechanisms of diseases. It requires integrating open data at a global scale. The Monarch Initiative advances these goals by developing open ontologies, semantic data models, and knowledge graphs for translational research. The Monarch App is
-
DELTEX E3 ligases ubiquitylate ADP-ribosyl modification on nucleic acids. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-24 Kang Zhu,Marcin J Suskiewicz,Chatrin Chatrin,Øyvind Strømland,Bryan W Dorsey,Vincent Aucagne,Dragana Ahel,Ivan Ahel
Although ubiquitylation had traditionally been considered limited to proteins, the discovery of non-proteinaceous substrates (e.g. lipopolysaccharides and adenosine diphosphate ribose (ADPr)) challenged this perspective. Our recent study showed that DTX2 E3 ligase efficiently ubiquitylates ADPr. Here, we show that the ADPr ubiquitylation activity is also present in another DELTEX family member, DTX3L
-
Biochemical and cellular insights into the Baz2B protein, a non-catalytic subunit of the chromatin remodeling complex. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-24 Matthias Breindl,Dominika Spitzer,Rūta Gerasimaitė,Visvaldas Kairys,Thomas Schubert,Ramona Henfling,Uwe Schwartz,Gražvydas Lukinavičius,Laura Manelytė
Baz2B is a regulatory subunit of the ATP-dependent chromatin remodeling complexes BRF1 and BRF5, which control access to DNA during DNA-templated processes. Baz2B has been implicated in several diseases and also in unhealthy ageing, however limited information is available on the domains and cellular roles of Baz2B. To gain more insight into the Baz2B function, we biochemically characterized the TAM
-
The Efg1-Bud22 dimer associates with the U14 snoRNP contacting the 5' rRNA domain of an early 90S pre-ribosomal particle. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-24 Olga Beine-Golovchuk,Martina Kallas,Ruth Kunze,Sabine Griesel,Jochen Baßler
The DEAD-box helicase Dbp4 plays an essential role during the early assembly of the 40S ribosome, which is only poorly understood to date. By applying the yeast two-hybrid method and biochemical approaches, we discovered that Dbp4 interacts with the Efg1-Bud22 dimer. Both factors associate with early pre-90S particles and smaller complexes, each characterized by a high presence of the U14 snoRNA. A
-
The replication enhancer crtS depends on transcription factor Lrp for modulating binding of initiator RctB to ori2 of Vibrio cholerae. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-24 Alexander Doan,Soniya Chatterjee,Roopa Kothapalli,Zaki Khan,Shaanit Sen,Noemi Kedei,Jyoti K Jha,Dhruba K Chattoraj,Revathy Ramachandran
Replication of Vibrio cholerae chromosome 2 (Chr2) initiates when the Chr1 locus, crtS (Chr2 replication triggering site) duplicates. The site binds the Chr2 initiator, RctB, and the binding increases when crtS is complexed with the transcription factor, Lrp. How Lrp increases the RctB binding and how RctB is subsequently activated for initiation by the crtS-Lrp complex remain unclear. Here we show
-
Cyclic di-GMP inhibits nitrate assimilation by impairing the antitermination function of NasT in Pseudomonas putida. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-24 Liang Nie,Yujie Xiao,Tiantian Zhou,Haoqi Feng,Meina He,Qingyuan Liang,Kexin Mu,Hailing Nie,Qiaoyun Huang,Wenli Chen
The ubiquitous bacterial second messenger cyclic diguanylate (c-di-GMP) coordinates diverse cellular processes through its downstream receptors. However, whether c-di-GMP participates in regulating nitrate assimilation is unclear. Here, we found that NasT, an antiterminator involved in nitrate assimilation in Pseudomonas putida, specifically bound c-di-GMP. NasT was essential for expressing the nirBD
-
Database resources of the National Center for Biotechnology Information Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-23 Eric W Sayers, Jeff Beck, Evan E Bolton, J Rodney Brister, Jessica Chan, Donald C Comeau, Ryan Connor, Michael DiCuccio, Catherine M Farrell, Michael Feldgarden, Anna M Fine, Kathryn Funk, Eneida Hatcher, Marilu Hoeppner, Megan Kane, Sivakumar Kannan, Kenneth S Katz, Christopher Kelly, William Klimke, Sunghwan Kim, Avi Kimchi, Melissa Landrum, Stacy Lathrop, Zhiyong Lu, Adriana Malheiro, Aron Marchler-Bauer
The National Center for Biotechnology Information (NCBI) provides online information resources for biology, including the GenBank® nucleic acid sequence database and the PubMed® database of citations and abstracts published in life science journals. NCBI provides search and retrieval operations for most of these data from 35 distinct databases. The E-utilities serve as the programming interface for
-
JANUS, a spliceosome-associated protein, promotes miRNA biogenesis in Arabidopsis Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-23 Mu Li, Huihui Yu, Bangjun Zhou, Lu Gan, Shengjun Li, Chi Zhang, Bin Yu
MicroRNAs (miRNAs) are important regulators of genes expression. Their levels are precisely controlled through modulating the activity of the microprocesser complex (MC). Here, we report that JANUS, a homology of the conserved U2 snRNP assembly factor in yeast and human, is required for miRNA accumulation. JANUS associates with MC components Dicer-like 1 (DCL1) and SERRATE (SE) and directly binds the
-
An improved method for the highly specific detection of transcription start sites Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-23 Masahide Seki, Yuta Kuze, Xiang Zhang, Ken-ichi Kurotani, Michitaka Notaguchi, Haruki Nishio, Hiroshi Kudoh, Takuya Suzaki, Satoko Yoshida, Sumio Sugano, Tomonao Matsushita, Yutaka Suzuki
Precise detection of the transcriptional start site (TSS) is a key for characterizing transcriptional regulation of genes and for annotation of newly sequenced genomes. Here, we describe the development of an improved method, designated ‘TSS-seq2.’ This method is an iterative improvement of TSS-seq, a previously published enzymatic cap-structure conversion method to detect TSSs in base sequences. By
-
Reactivation of the G1 enhancer landscape underlies core circuitry addiction to SWI/SNF Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-23 Katerina Cermakova, Ling Tao, Milan Dejmek, Michal Sala, Matthew D Montierth, Yuen San Chan, Ivanshi Patel, Courtney Chambers, Mario Loeza Cabrera, Dane Hoffman, Ronald J Parchem, Wenyi Wang, Radim Nencka, Eveline Barbieri, H Courtney Hodges
Several cancer core regulatory circuitries (CRCs) depend on the sustained generation of DNA accessibility by SWI/SNF chromatin remodelers. However, the window when SWI/SNF is acutely essential in these settings has not been identified. Here we used neuroblastoma (NB) cells to model and dissect the relationship between cell-cycle progression and SWI/SNF ATPase activity. We find that SWI/SNF inactivation
-
Modular cytosine base editing promotes epigenomic and genomic modifications. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-22 Julian Weischedel,Laurence Higgins,Sally Rogers,Anna Gramalla-Schmitz,Paulina Wyrzykowska,Simone Borgoni,Thomas MacCarthy,Richard Chahwan
Prokaryotic and eukaryotic adaptive immunity differ considerably. Yet, their fundamental mechanisms of gene editing via Cas9 and activation-induced deaminase (AID), respectively, can be conveniently complimentary. Cas9 is an RNA targeted dual nuclease expressed in several bacterial species. AID is a cytosine deaminase expressed in germinal centre B cells to mediate genomic antibody diversification
-
Interactome of intact chromatosome variants with site-specifically ubiquitylated and acetylated linker histone H1.2. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-22 Philip Saumer,Martin Scheffner,Andreas Marx,Florian Stengel
Post-translational modifications (PTMs) of histones have fundamental effects on chromatin structure and function. While the impact of PTMs on the function of core histones are increasingly well understood, this is much less the case for modifications of linker histone H1, which is at least in part due to a lack of proper tools. In this work, we establish the assembly of intact chromatosomes containing
-
Structural analysis of PLD3 reveals insights into the mechanism of lysosomal 5' exonuclease-mediated nucleic acid degradation. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-22 Yvette Roske,Cedric Cappel,Nils Cremer,Patrick Hoffmann,Tomas Koudelka,Andreas Tholey,Udo Heinemann,Oliver Daumke,Markus Damme
The phospholipase D (PLD) family is comprised of enzymes bearing phospholipase activity towards lipids or endo- and exonuclease activity towards nucleic acids. PLD3 is synthesized as a type II transmembrane protein and proteolytically cleaved in lysosomes, yielding a soluble active form. The deficiency of PLD3 leads to the slowed degradation of nucleic acids in lysosomes and chronic activation of nucleic
-
Cross-species investigation into the requirement of XPA for nucleotide excision repair. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-22 Cansu Kose,Xuemei Cao,Evan B Dewey,Mustafa Malkoç,Ogün Adebali,Jeff Sekelsky,Laura A Lindsey-Boltz,Aziz Sancar
After reconstitution of nucleotide excision repair (excision repair) with XPA, RPA, XPC, TFIIH, XPF-ERCC1 and XPG, it was concluded that these six factors are the minimal essential components of the excision repair machinery. All six factors are highly conserved across diverse organisms spanning yeast to humans, yet no identifiable homolog of the XPA gene exists in many eukaryotes including green plants
-
Splitting the yeast centromere by recombination. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-22 Stanislav G Kozmin,Margaret Dominska,Dao-Qiong Zheng,Thomas D Petes
Although fusions between the centromeres of different human chromosomes have been observed cytologically in cancer cells, since the centromeres are long arrays of satellite sequences, the details of these fusions have been difficult to investigate. We developed methods of detecting recombination within the centromeres of the yeast Saccharomyces cerevisiae (intercentromere recombination). These events
-
Direct visualization of replication and R-loop collision using single-molecule imaging. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-22 Subin Kim,Woo Hee Shin,Yujin Kang,Hongtae Kim,Ja Yil Lee
R-loops are three-stranded nucleic acid structures that can cause replication stress by blocking replication fork progression. However, the detailed mechanism underlying the collision of DNA replication forks and R-loops remains elusive. To investigate how R-loops induce replication stress, we use single-molecule fluorescence imaging to directly visualize the collision of replicating Phi29 DNA polymerase
-
A novel HPV16 splicing enhancer critical for viral oncogene expression and cell immortalization. Nucleic Acids Res. (IF 14.9) Pub Date : 2023-11-22 Johanna Jönsson,Lianqing Wang,Naoko Kajitani,Stefan Schwartz
High-risk carcinogenic human papillomaviruses (HPVs), e.g. HPV16, express the E6 and E7 oncogenes from two mRNAs that are generated in a mutually exclusive manner by splicing. The HPV16 E7 mRNA, also known as the E6*I/E7 mRNA, is produced by splicing between splice sites SD226 and SA409, while E6 mRNAs retain the intron between these splice sites. We show that splicing between HPV16 splice sites SD226