IF 4.2 3区生物学

RNA Pub Date : 2025-06-16 DOI: 10.1261/rna.080222.124

Guo-Shi Chai, Hong-Xuan Chen, Dong-Zhao Ma, Ze-Hui Ren, Xue-Hong Liu, Zhang Zhang, Guan-Zheng Luo

{"title":"Comprehensive analysis of m6A-seq data reveals distinct features of conserved and unique m6A sites in mammals.","authors":"Guo-Shi Chai, Hong-Xuan Chen, Dong-Zhao Ma, Ze-Hui Ren, Xue-Hong Liu, Zhang Zhang, Guan-Zheng Luo","doi":"10.1261/rna.080222.124","DOIUrl":"10.1261/rna.080222.124","url":null,"abstract":"N6-methyladenine (m6A) stands out as the most prevalent internal chemical modification on mammalian mRNA, playing a vital role in diverse biological processes. However, the characteristics of m6A across different cell lines and tissues remain poorly understood. In this study, we systematically evaluated 193 published m6A-seq data sets using newly established quality metrics, identifying ∼1.5 million high-confidence m6A sites in human and mouse. By categorizing m6A sites into different consistency levels, we observed that high-consistency m6A sites were enriched near mRNA stop codons and lncRNA 5' ends, exhibited stronger interactions with canonical m6A-binding proteins, and contributed to mRNA/lncRNA expression homeostasis. Furthermore, the promoters of genes marked by these consistent sites exhibited higher CpG density, with METTL3 preferentially binding to these regions. Conversely, low-consistency or unique m6A sites were enriched near mRNA start codons and distributed evenly across lncRNA, interacting with newly discovered m6A-binding proteins. These findings enhance our understanding of the diverse characteristics and potential functional roles of m6A in mammals.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1013-1027"},"PeriodicalIF":4.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamic RNA binding and unfolding by nonsense-mediated mRNA decay factor UPF2. 无义介导的mRNA衰变因子UPF2的动态RNA结合和展开。

IF 4.2 3区生物学

RNA Pub Date : 2025-06-16 DOI: 10.1261/rna.080300.124

Jenn-Yeu A Szeto, Mirella Vivoli Vega, Justine Mailliot, George Orriss, Lingling Sun, Joshua C Bufton, Kyle T Powers, Sathish K N Yadav, Imre Berger, Christiane Schaffitzel

{"title":"Dynamic RNA binding and unfolding by nonsense-mediated mRNA decay factor UPF2.","authors":"Jenn-Yeu A Szeto, Mirella Vivoli Vega, Justine Mailliot, George Orriss, Lingling Sun, Joshua C Bufton, Kyle T Powers, Sathish K N Yadav, Imre Berger, Christiane Schaffitzel","doi":"10.1261/rna.080300.124","DOIUrl":"10.1261/rna.080300.124","url":null,"abstract":"Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance pathway involved in translational control and gene expression regulation. Core NMD factors up-frameshift proteins UPF1, UPF2, and UPF3B are conserved from yeast to humans and essential to target mRNAs with a premature stop codon for decay. UPF2 binding to UPF1 activates UPF1's ATPase and helicase activities, and UPF2 binding to UPF3B is important for its association with the exon junction complex and efficient NMD. However, UPF2's association with RNA remains largely uncharacterized. Here, we analyze nucleic acid binding, identifying the first and third MIF4G domains of UPF2 as main RNA-/DNA-binding modules. We find that UPF2's MIF4G domain-3 has RNA annealing activity, while full-length UPF2 unfolds our reporter hairpin RNA structure. We show that UPF2 preferentially binds and stabilizes single-stranded RNA (ss-RNA) in a sequence-independent manner. Concomitant to ss-RNA binding, UPF2 undergoes a distinct conformational change in its otherwise highly dynamic structure. UPF2's RNA binding and unfolding activity may support UPF1's helicase and messenger ribonucleoprotein remodeling activity and, in combination with UPF3B, stabilize UPF1's association with nonsense mRNA.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"933-948"},"PeriodicalIF":4.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative analyses of disease-linked missense mutations in the RNA exosome modeled in budding yeast reveal distinct functional consequences in translation. 在出芽酵母中建模的RNA外泌体中与疾病相关的错义突变的比较分析揭示了翻译中不同的功能后果。

IF 4.2 3区生物学

RNA Pub Date : 2025-06-16 DOI: 10.1261/rna.080447.125

Maria C Sterrett, Lauryn A Cureton, Lauren N Cohen, Ambro van Hoof, Sohail Khoshnevis, Milo B Fasken, Anita H Corbett, Homa Ghalei

{"title":"Comparative analyses of disease-linked missense mutations in the RNA exosome modeled in budding yeast reveal distinct functional consequences in translation.","authors":"Maria C Sterrett, Lauryn A Cureton, Lauren N Cohen, Ambro van Hoof, Sohail Khoshnevis, Milo B Fasken, Anita H Corbett, Homa Ghalei","doi":"10.1261/rna.080447.125","DOIUrl":"10.1261/rna.080447.125","url":null,"abstract":"The RNA exosome is a multisubunit, evolutionarily conserved ribonuclease complex that is essential for processing, decay, and surveillance of many cellular RNAs. Missense mutations in genes encoding the structural subunits of the RNA exosome complex cause a diverse range of diseases, collectively known as RNA exosomopathies, often involving neurological and developmental defects. The varied symptoms suggest that different mutations lead to distinct in vivo consequences. To investigate these functional consequences and distinguish whether they are unique to each RNA exosomopathy mutation, we generated a collection of in vivo models by introducing pathogenic missense mutations in orthologous Saccharomyces cerevisiae genes. Comparative RNA-seq analysis assessing broad transcriptomic changes in each mutant model revealed that three yeast mutant models, rrp4-G226D, rrp40-W195R, and rrp46-L191H, which model mutations in the genes encoding EXOSC2, EXOSC3, and EXOSC5, respectively, had the largest transcriptomic differences. While some transcriptomic changes, particularly in transcripts related to ribosome biogenesis, were shared among mutant models, each mutation also induced unique transcriptomic changes. Thus, our data suggest that while there are some shared consequences, there are also distinct differences in RNA exosome function by each variant. Assessment of ribosome biogenesis and translation defects in the three models revealed distinct differences in polysome profiles. Collectively, our results provide the first comparative analyses of RNA exosomopathy mutant models and suggest that different RNA exosome gene mutations result in in vivo consequences that are both unique and shared across each variant, providing further insight into the biology underlying each distinct pathology.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"988-1012"},"PeriodicalIF":4.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum: Exploring the therapeutic potential of modulating nonsense-mediated mRNA decay. 勘误：探索调节无义介导的mRNA衰变的治疗潜力。

IF 4.2 3区生物学

RNA Pub Date : 2025-06-16 DOI: 10.1261/rna.080521.125

Mary McMahon, Lynne E Maquat

引用次数: 0

Evaluating computational tools for protein-coding sequence detection: Are they up to the task? 评估蛋白质编码序列检测的计算工具：它们能胜任任务吗？

IF 4.2 3区生物学

RNA Pub Date : 2025-06-11 DOI: 10.1261/rna.080416.125

D J Champion, Ting-Hsuan Chen, Susan Thomson, Michael A Black, Paul P Gardner

{"title":"Evaluating computational tools for protein-coding sequence detection: Are they up to the task?","authors":"D J Champion, Ting-Hsuan Chen, Susan Thomson, Michael A Black, Paul P Gardner","doi":"10.1261/rna.080416.125","DOIUrl":"https://doi.org/10.1261/rna.080416.125","url":null,"abstract":"Background: Detecting protein coding genes in nucleotide sequences is a significant challenge for understanding genome and transcriptome function, yet the reliability of bioinformatic tools for this task remains largely unverified. This is despite some tools being available for several decades, and widely used for genome and transcriptome annotation.Results: We perform an assessment of nucleotide sequence and alignment-based de novo protein-coding detection tools. The controls we use exclude any previous training dataset and include coding exons as a positive set and length-matched intergenic and shuffled sequences as negative sets. Our work demonstrates that several widely used tools are neither accurate nor computationally efficient for the protein-coding sequence detection problem. In fact, just three of nine tools significantly outperformed a naive scoring scheme. Furthermore, we note a high discrepancy between self-reported accuracies and the accuracy achieved in our study. Our results show that the extra dimension from conserved and variable nucleotides in alignments have a significant advantage over single sequence approaches.Conclusions: These results highlight significant limitations in existing protein-coding annotation tools that are widely used for lncRNA annotation. This shows a need for more robust and efficient approaches to training and assessing the performance of tools for identifying protein-coding sequences. Our study paves the way for future advancements in comparative genomic approaches and we hope will popularise more robust approaches to genome and transcriptome annotation.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural analysis of the lncRNA SChLAP1 reveals protein binding interfaces and a conformationally heterogenous retroviral insertion. lncRNA SChLAP1的结构分析揭示了蛋白质结合界面和构象异质逆转录病毒插入。

IF 4.2 3区生物学

RNA Pub Date : 2025-06-11 DOI: 10.1261/rna.080488.125

James P Falese, Emily J McFadden, Christopher A d'Inzeo, Amanda E Hargrove

{"title":"Structural analysis of the lncRNA SChLAP1 reveals protein binding interfaces and a conformationally heterogenous retroviral insertion.","authors":"James P Falese, Emily J McFadden, Christopher A d'Inzeo, Amanda E Hargrove","doi":"10.1261/rna.080488.125","DOIUrl":"https://doi.org/10.1261/rna.080488.125","url":null,"abstract":"The lncRNA Second Chromosome Locus Associated with Prostate 1 (SChLAP1) was previously identified as a predictive biomarker and potential driver of aggressive prostate cancer. Recent work suggested that SChLAP1 may bind the SWI/SNF chromatin remodeling complex to promote prostate cancer metastasis, though the exact role of SWI/SNF recognition is debated. To date, there are no detailed biochemical studies of apo SChLAP1 or SChLAP1:protein complexes. Herein, we report the first secondary structure model of SChLAP1 using SHAPE-MaP in vitro, in cellulo, and ex cellulo (protein-free). Comparison of the ex cellulo and in cellulo data via ΔSHAPE identified putative protein binding regions within SChLAP1. In addition, phylogenetic analysis revealed that SChLAP1 is a primate-conserved lncRNA, with two exons significantly derived from primate-specific retroviral insertions. In particular, we characterized a complex structural landscape in a protein binding region at the 3'end of SChLAP1 derived from a THE1B-type retroviral insertion, suggesting a role for an exapted RNA structure in SChLAP1:protein recognition and prostate cancer progression. Lastly, pulldowns of SChLAP1 substructures enabled identification of previously unestablished SChLAP1-interacting proteins. This work lays the foundation for future efforts to selectively target and disrupt SChLAP1 structures and/or protein interfaces and to develop new therapeutic avenues in prostate cancer treatment.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel ADAR2 variants in children with seizures, intellectual disability and motor delay have reduced RNA editing. 患有癫痫、智力残疾和运动迟缓儿童的新型ADAR2变异减少了RNA编辑。

IF 4.2 3区生物学

RNA Pub Date : 2025-06-06 DOI: 10.1261/rna.080600.125

Qiupei Du, Anna Cherian, Raymond J Louie, Giulia Barcia, Natasha Rudy, Rima Nabbout, Eugenie Sarda, Maelle Charpie, Wesley G Patterson, Liam Peter Keegan, Mary A O'Connell

{"title":"Novel ADAR2 variants in children with seizures, intellectual disability and motor delay have reduced RNA editing.","authors":"Qiupei Du, Anna Cherian, Raymond J Louie, Giulia Barcia, Natasha Rudy, Rima Nabbout, Eugenie Sarda, Maelle Charpie, Wesley G Patterson, Liam Peter Keegan, Mary A O'Connell","doi":"10.1261/rna.080600.125","DOIUrl":"https://doi.org/10.1261/rna.080600.125","url":null,"abstract":"The ADARB1 gene encodes the ADAR2 RNA editing enzyme, which edits the GRIA2 transcript Q/R editing site with almost 100% efficiency in the nervous system. The edited GRIA2R transcript encodes the GLUA2 R subunit isoform of tetrameric AMPA receptors, which is essential to prevent seizures associated with aberrantly elevated AMPA receptor cation permeability. Rare biallelic variants in ADARB1 cause severe infant and childhood seizures and developmental delays in seven cases we previously described. Here, we report two new homozygous ADARB1 variants and study ADAR2 variant editing activities at the GRIA2 Q/R site and other editing sites in cell cultures. One new variant in the second dsRNA binding domain (dsRBD II) retains up to 60% editing activity, whereas another, in the deaminase domain, eliminates RNA editing activity. Reduced GRIA2 Q/R site editing increases AMPA receptor permeability by upregulating the expression of the GLUA2 Q isoform and reducing overall GLUA2 subunit levels, resulting in AMPA receptors that lack GLUA2 and are calcium-permeable. Since failure to edit the GRIA2 Q/R site leads to failure of intron 11 splicing, we also examined the effects of ADAR2 variants on the splicing of a mouse Gria2-based reporter and concluded that ADAR2 variants affect splicing only through their effects on RNA editing activity. To expand the number of variants in ADARB1, some variants reported in ClinVar have also been analysed by in silico methods to predict which are likely to be most deleterious and associated with seizures in patients.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RNA G-quadruplex structure targeting and imaging: recent advances and future directions. RNA g -四重体结构靶向与成像：最新进展及未来发展方向。

IF 4.2 3区生物学

RNA Pub Date : 2025-06-05 DOI: 10.1261/rna.080587.125

Tian-Ying Wu, Hill Lam Lau, Rachelle J Santoso, Chun Kit Kwok

{"title":"RNA G-quadruplex structure targeting and imaging: recent advances and future directions.","authors":"Tian-Ying Wu, Hill Lam Lau, Rachelle J Santoso, Chun Kit Kwok","doi":"10.1261/rna.080587.125","DOIUrl":"https://doi.org/10.1261/rna.080587.125","url":null,"abstract":"RNA guanine (G)-quadruplexes (rG4s) are non-canonical structures formed by G-rich RNA sequences, and have been demonstrated to play critical roles in various biological events, including translation, transcription, RNA processing, and other cellular functions. In contrast to DNA G-quadruplexes (dG4s), research on rG4s has been relatively limited until recently. Recent advances in targeting and imaging of rG4s have opened new avenues for understanding their functional significance and therapeutic potential. In this review, we summarize the innovative platforms and tools being developed to target rG4s, highlight the novel and important imaging probes that have been generated and applied for rG4 structure visualization in different biological contexts, and discuss the challenges and perspectives for further advancing these technologies and toolsets to facilitate rG4 targeting and imaging with greater precision and resolution across the tree of life. These scientific developments and breakthroughs will enable the discovery of new biological insights regarding rG4s and help decipher their molecular mechanisms and implications for health and disease.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rho-dependent transcription termination: mechanisms and roles in bacterial fitness and adaptation to environmental changes. rho依赖性转录终止：细菌适应度和适应环境变化的机制和作用。

IF 4.2 3区生物学

RNA Pub Date : 2025-06-03 DOI: 10.1261/rna.080486.125

Thuy Duong Do, Nara Figueroa-Bossi, Johnathan C Black, Eric Eveno, Mildred Delaleau, Lionello Bossi, Marc Boudvillain

{"title":"Rho-dependent transcription termination: mechanisms and roles in bacterial fitness and adaptation to environmental changes.","authors":"Thuy Duong Do, Nara Figueroa-Bossi, Johnathan C Black, Eric Eveno, Mildred Delaleau, Lionello Bossi, Marc Boudvillain","doi":"10.1261/rna.080486.125","DOIUrl":"https://doi.org/10.1261/rna.080486.125","url":null,"abstract":"The bacterial transcription termination factor Rho is a rare example of an RNA helicase that functions as a ring-shaped ATP-powered six-subunit motor. Recent studies have linked Rho's distinctive architecture to a variety of regulatory mechanisms that shape the bacterial transcriptome at the global scale and control the transcription of individual genes in a context-dependent manner. In this review, we provide a comprehensive overview of the molecular mechanisms by which Rho triggers transcription termination. We examine the two prevailing modes of Rho's action: the \"catch-up\" mode, where Rho actively translocates along RNA and collides with the RNA polymerase to terminate transcription, and the \"stand-by\" mode where Rho, recruited by transcription elongation factor NusG, remains poised to engage RNA polymerase at specific sites or under particular constraints. Additionally, we highlight Rho's interplay with nucleoid-structuring protein H-NS in the regulation of bacterial chromatin transcription, as well as the crucial role played by Rho in the conditional regulation of specific genomic loci. We discuss how these mechanisms contribute to the fine-tuning of gene activity and integrate into broader regulatory networks, supporting bacterial adaptation to environmental changes and resilience to external challenges.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human CCR4 deadenylase homolog Angel1 is a Non-Stop mRNA Decay factor. 人类CCR4 deadenylase同源物Angel1是一个不间断的mRNA衰变因子。

IF 4.2 3区生物学

RNA Pub Date : 2025-05-29 DOI: 10.1261/rna.080399.125

Tim Nicholson-Shaw, Megan E Dowdle, Yasmeen Ajaj, Mark Perelis, Amit Fulzele, Gene W Yeo, Eric J Bennett, Jens Lykke-Andersen

引用次数: 0

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