IF 4.2 3区生物学

RNA Pub Date : 2025-06-16 DOI: 10.1261/rna.080442.125

Charles P Rabolli, Anindhya S Das, Volha A Golubeva, Jop H van Berlo, Federica Accornero

引用次数: 0

SMDesigner: a program to design sequence mutations to assess RNA structure. SMDesigner：设计序列突变以评估RNA结构的程序。

IF 4.2 3区生物学

RNA Pub Date : 2025-06-16 DOI: 10.1261/rna.080267.124

Lijuan Hou, Meryem Raies, Kadidia Dite Selly N'Diaye, Jonathan Perreault

{"title":"SMDesigner: a program to design sequence mutations to assess RNA structure.","authors":"Lijuan Hou, Meryem Raies, Kadidia Dite Selly N'Diaye, Jonathan Perreault","doi":"10.1261/rna.080267.124","DOIUrl":"10.1261/rna.080267.124","url":null,"abstract":"The structure of RNA is critical to its function. The advancement of structure prediction algorithms and deep sequencing technology has led to the discovery of numerous conserved RNA structures. However, functional analysis of these sequences is lagging behind the rate of novel RNAs' predictions. Traditionally, mutations are designed to alter the structure of RNA and tested individually to assess function. We developed a program for the large-scale characterization of the structure/function relationship in multiple RNAs. Structure Mutation Designer (SMDesigner) automatically selects both disruptive and compensatory mutations according to inputted structural information. As proof of concept, we designed mutations for riboswitches with SMDesigner and experimentally assessed six of these riboswitches and their mutant sequences using an in-line probing assay to verify the effects on their structure and function. The in-line probing results show expected changes in five of six sequence structure patterns, confirming that SMDesigner can be useful to explore RNA structure and subsequent function. SMDesigner can be download at: https://github.com/lilihou/SMDesigner_0.1/tree/main/dist.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"874-884"},"PeriodicalIF":4.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024136","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

Structures of RNA phosphotransferase Tpt1 reveal distinct binding modes for an RNA 2'-PO₄ splice junction versus a 5'-PO₄ mononucleotide. RNA磷酸转移酶Tpt1的结构揭示了RNA 2'-PO4剪接与5'-PO4单核苷酸的不同结合模式。

IF 4.2 3区生物学

RNA Pub Date : 2025-06-16 DOI: 10.1261/rna.080444.125

Agata Jacewicz, Masad J Damha, Stewart Shuman

引用次数: 0

Regulation of cardiac hypertrophy by RNA readers. RNA阅读器对心肌肥厚的调控。

IF 4.2 3区生物学

RNA Pub Date : 2025-06-16 DOI: 10.1261/rna.080557.125

Sarah Costantino, Francesco Paneni

引用次数: 0

Unraveling unbreakable hairpins: characterizing RNA secondary structures that are persistent after dinucleotide shuffling. 解开牢不可破的发夹：表征二核苷酸洗牌后持续存在的RNA二级结构。

IF 4.2 3区生物学

RNA Pub Date : 2025-06-16 DOI: 10.1261/rna.080176.124

Alyssa A Pratt, David A Hendrix

{"title":"Unraveling unbreakable hairpins: characterizing RNA secondary structures that are persistent after dinucleotide shuffling.","authors":"Alyssa A Pratt, David A Hendrix","doi":"10.1261/rna.080176.124","DOIUrl":"10.1261/rna.080176.124","url":null,"abstract":"The sequence of nucleotides that make up an RNA determines its structure, which determines its function. The RNA hairpin, also known as a stem-loop, is a ubiquitous and fundamental feature of RNA secondary structure. A common method of randomizing an RNA sequence is dinucleotide shuffling with the Altschul-Erickson algorithm, which preserves the dinucleotide content of the sequence. This algorithm generates randomized sequences by sampling Eulerian paths through the de Bruijn graph representation of the original sequence. We identified a subset of RNA hairpins in the bpRNA-1m meta-database that always form hairpins after repeated application of dinucleotide shuffling. We investigated these \"unbreakable hairpins\" and found several common properties. First, we found that unbreakable hairpins had on average similar folding energies compared to other hairpins of similar lengths, although they frequently contained ultra-stable hairpin loops. We found that they tend to be split by purines and pyrimidines on opposite sides of the stem. Furthermore, we found that this specific sequence feature restricts the number of distinct Eulerian paths through their de Bruijn graph representation, resulting in a small number of distinguishable dinucleotide-shuffled sequences. Beyond this algorithmic means of identification, these distinct sequences may have biological significance because we found that a significant percentage occur in a specific location of 16S ribosomal RNAs.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"885-895"},"PeriodicalIF":4.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034645","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

The influence of downstream structured elements within mRNA on the dynamics of intersubunit rotation in ribosomes. mRNA下游结构元件对核糖体亚基间旋转动力学的影响。

IF 4.2 3区生物学

RNA Pub Date : 2025-06-16 DOI: 10.1261/rna.080291.124

Bassem Shebl, Anna Pavlova, Preston Kellenberger, Dongmei Yu, Drew E Menke, James C Gumbart, Peter V Cornish

{"title":"The influence of downstream structured elements within mRNA on the dynamics of intersubunit rotation in ribosomes.","authors":"Bassem Shebl, Anna Pavlova, Preston Kellenberger, Dongmei Yu, Drew E Menke, James C Gumbart, Peter V Cornish","doi":"10.1261/rna.080291.124","DOIUrl":"10.1261/rna.080291.124","url":null,"abstract":"Proper codon/anticodon pairing within the ribosome necessitates linearity of the transcript. Any structures formed within a messenger RNA (mRNA) must be unwound before the respective codon is interpreted. Linearity, however, is not always the norm; some intricate structures within mRNA are able to exert unique ribosome/mRNA interactions to regulate translation. Intrinsic kinetic and thermal stability in many of these structures are efficient in slowing translation causing pausing of the ribosome. Altered translation kinetics arising from atypical interactions have been shown to affect intersubunit rotation. Here, we employ single-molecule Förster resonance energy transfer (smFRET) to observe changes in intersubunit rotation of the ribosome as it approaches downstream structured nucleic acid. The emergence of the hyperrotated state is critically dependent on the distance between downstream structure and the ribosome, suggesting interactions with the helicase center are allosterically coupled to intersubunit rotation. Further, molecular dynamics (MD) simulations were performed to determine ribosomal protein/mRNA interactions that may play a pivotal role in helicase activity and ultimately unwinding of downstream structure.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"973-987"},"PeriodicalIF":4.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028309","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

Crystallographic and cryoEM analyses reveal SARS-CoV-2 SL5 is a mobile T-shaped four-way junction with deep pockets. 晶体学和低温电镜分析显示，SARS-CoV-2 SL5是一个具有深口袋的移动t形四向结。

IF 4.2 3区生物学

RNA Pub Date : 2025-06-16 DOI: 10.1261/rna.080413.125

Christopher P Jones, Adrian R Ferré-D'Amaré

{"title":"Crystallographic and cryoEM analyses reveal SARS-CoV-2 SL5 is a mobile T-shaped four-way junction with deep pockets.","authors":"Christopher P Jones, Adrian R Ferré-D'Amaré","doi":"10.1261/rna.080413.125","DOIUrl":"10.1261/rna.080413.125","url":null,"abstract":"Stem-loop 5 (SL5) is a structural element that is conserved across coronavirus genomic RNAs. It spans the start codon from which the long ORF1 is translated in full-length viral RNA. Phylogenetic conservation indicates that it is comprised of four paired elements, but the specific 3D arrangement of these helices has remained unknown. Now, we have solved the crystal structure of SL5 from SARS-CoV-2 at 3.3 Å resolution, finding that the RNA adopts a T-shaped four-way junction fold in which two coaxial stacks of two helices each pack orthogonally. This arrangement results in deep pockets at the helical junction, where cations bind. Except for limited interactions in this region, the structure is remarkable for the paucity of tertiary contacts. We confirmed the stability of this fold in solution by FRET and carried out single-particle cryogenic-sample electron microscopy (cryoEM). The resulting ∼5 Å resolution cryoEM map, and 3D variability analysis, suggest conformational flexibility at the junction. In vitro translation of structure-guided mutants demonstrated that SL5 inhibits protein synthesis. Thus, it is likely that SL5 recruits additional factors in vivo. This, and its characteristic clefts at the four-way junction, make SL5 an attractive target for the discovery of RNA-targeted antiviral small molecules.","PeriodicalId":21401,"journal":{"name":"RNA","volume":"31 7","pages":"949-960"},"PeriodicalIF":4.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317846","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

Comprehensive analysis of m6A-seq data reveals distinct features of conserved and unique m6A sites in mammals. 对m6A-seq数据的综合分析揭示了哺乳动物中保守和独特的m6A位点的明显特征。

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

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

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