IF 4.3 3区生物学

RNA Pub Date : 2026-06-16 DOI: 10.1261/rna.081007.126

Lauren Bednor, Aleksei Innokentev, Ana M Sanchez, Angela Sem, Beate Schwer, Stewart Shuman

{"title":"Nuclear basket subunits Nup211 and Rsm1 influence RNA 3'-processing and transcription termination in fission yeast.","authors":"Lauren Bednor, Aleksei Innokentev, Ana M Sanchez, Angela Sem, Beate Schwer, Stewart Shuman","doi":"10.1261/rna.081007.126","DOIUrl":"10.1261/rna.081007.126","url":null,"abstract":"The fission yeast phosphate acquisition (PHO) regulon is repressed under phosphate-replete conditions by upstream lncRNA-mediated transcriptional interference. Inositol-1-pyrophosphates control PHO gene expression via their action as agonists of precocious PHO lncRNA 3'-processing/termination. Inositol pyrophosphatase-inactivating asp1-STF mutations that increase inositol-1-pyrophosphates elicit derepression of the PHO genes and a severe growth defect in YES medium. Previous studies demonstrated suppression of inositol pyrophosphate toxicosis by loss-of-function and hypomorphic mutations in 11 of the 14 subunits of the fission yeast cleavage and polyadenylation factor (CPF) complex. Here, we report the identification and characterization of mutations in the Nup211 and Rsm1 subunits of the nuclear basket of the nuclear pore complex that suppress inositol pyrophosphate toxicosis. We localize Nup211's activity in asp1-STF toxicosis to the C-terminal segment that forms a globular module appended to the Nup211 coiled-coil of the nuclear basket strut. A triple-alanine mutation of a conserved Nup211 1821RDD1823 peptide sufficed to suppress asp1-STF toxicosis. We find that (i) induced overexpression of the Nup211 C-terminal segment is itself toxic to fission yeast and that this toxicity was abolished by the RDD-AAA mutation and (ii) Nup211 C-terminal truncation confers synthetic growth defects when combined with loss-of-function mutations in CPF subunits Ppn1, Swd22, and Ssu72. Our results implicate the Nup211 C terminus as part of a protein-protein interface that abets 3'-processing/termination.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1101-1114"},"PeriodicalIF":4.3,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676337","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

A 2025 meeting report from the Venice lagoon: International graduate program RNAmed - Future Leaders in RNA-based Medicine meets on San Servolo. 2025年威尼斯泻湖会议报告：国际研究生项目“rna - rna医学的未来领导者”在圣塞沃罗举行会议。

IF 4.3 3区生物学

RNA Pub Date : 2026-06-16 DOI: 10.1261/rna.080962.126

Jörg Vogel, Charlotte Kamm, Giorgia Gerolimetto, Pranjal Meel, Alexandre Trubert, Stina Rademacker, Christian Fröschel

{"title":"A 2025 meeting report from the Venice lagoon: International graduate program RNAmed - Future Leaders in RNA-based Medicine meets on San Servolo.","authors":"Jörg Vogel, Charlotte Kamm, Giorgia Gerolimetto, Pranjal Meel, Alexandre Trubert, Stina Rademacker, Christian Fröschel","doi":"10.1261/rna.080962.126","DOIUrl":"10.1261/rna.080962.126","url":null,"abstract":"RNAmed - Future Leaders in RNA-based Medicine is a unique graduate training program in the area of RNA-based medicine. Financed by the Free State of Bavaria, Germany, it is jointly run by several universities and research institutes from Würzburg, Regensburg, and Munich. It aspires to equip doctoral students with a comprehensive idea of RNA therapeutics, spanning fundamental biology, translational research, clinical application, regulation, ethics, and societal implications. This integrative approach is meant to cultivate exceptional qualifications for careers across academia, industry, and policy. The RNAmed program held its 2025 annual retreat on San Servolo (Venice, Italy), with a total of 40 doctoral researchers, principal investigators (PIs), and invited guests from academia and pharmaceutical industry attending. The three-day program combined keynotes, student presentations, flash talks, a career panel, and topic-table discussions of advances and challenges across RNA therapeutics to catalyze exchange and collaboration. Presentations highlighted emerging directions for antisense strategies, circular RNAs, delivery technologies, and AI-enabled molecular design, reflecting the program's cross-disciplinary nature. Discussions emphasized shared priorities such as clear experimental standards, robust delivery solutions, and stronger academia-industry ties to accelerate safe, effective RNA medicines. Updates on RNAmed's growth and extended funding underscored its mission to develop talent through integrated scientific and professional training. Overall, the retreat strengthened a network of early-career scientists and mentors committed to advancing RNA-based modalities from concept to clinic.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"983-992"},"PeriodicalIF":4.3,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13270997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514461","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

Direct RNA-seq provides evidence for an antiterminator function of the yeast Hrp1 protein on RNA polymerase II transcripts. 直接RNA-seq为酵母Hrp1蛋白在RNA聚合酶II转录物上的抗终结者功能提供了证据。

IF 4.3 3区生物学

RNA Pub Date : 2026-06-16 DOI: 10.1261/rna.080781.125

Emma C Goguen, Kylie A Zawisza, David A Brow

{"title":"Direct RNA-seq provides evidence for an antiterminator function of the yeast Hrp1 protein on RNA polymerase II transcripts.","authors":"Emma C Goguen, Kylie A Zawisza, David A Brow","doi":"10.1261/rna.080781.125","DOIUrl":"10.1261/rna.080781.125","url":null,"abstract":"Hrp1/Nab4 is an essential nuclear RNA-binding protein that was first identified in the yeast Saccharomyces cerevisiae as a cleavage and polyadenylation factor for mRNAs, CF1B, but was later shown to promote termination of some short, noncoding transcripts via the \"NNS\" termination pathway. Hrp1 binds (UA)n repeats found in both mRNA 3' UTRs and short noncoding RNA terminators, but its function in 3'-end formation is not fully understood. Our past microarray transcriptome analysis of the heat-sensitive hrp1-7 allele suggested Hrp1 functions in antitermination of RNA polymerase II (RNAP II) on protein-coding genes. The hrp1-7 allele has four substitutions, and one, M191T, was shown to be primarily responsible for NNS terminator readthrough. Here we show that Hrp1-7 protein has a threefold and Hrp1-M191T a 1.5-fold decreased affinity for (UA)4 in vitro. We used nanopore direct RNA sequencing to assess the transcriptome-wide effects of hrp1-7 and hrp1-M191T, which identified new examples of Hrp1-dependent small nucleolar RNA terminators and mRNA attenuators (regulatory terminators in the 5' UTR and ORF). For some genes, including HRP1, attenuated transcript reads outnumber the corresponding mRNA reads in exponentially growing wild-type cells. We also observed widespread changes in mRNA poly(A) site selection. In the hrp1-M191T strain, the poly(A) site shifts are mostly downstream, while in the hrp1-7 strain, upstream and downstream shifts are more similar in frequency. Our results are consistent with a model in which one or more of the four substitutions in hrp1-7 weaken the affinity of Hrp1 for the RNAP II elongation complex, promoting premature termination, while others interfere with its recognition of terminator sequences, promoting terminator readthrough.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1115-1128"},"PeriodicalIF":4.3,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779713","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

Development of Universal Mass Exclusion List (UMEL) for RNA modification mapping. 用于RNA修饰定位的通用质量排除表（UMEL）的开发。

IF 4.3 3区生物学

RNA Pub Date : 2026-06-16 DOI: 10.1261/rna.080901.125

Asif Rayhan, Patrick A Limbach, Balasubrahmanyam Addepalli

引用次数: 0

Dual role of 3' UTR length in modulating translation termination efficiency. 3' UTR长度在调制转译终止效率中的双重作用。

IF 4.3 3区生物学

RNA Pub Date : 2026-06-16 DOI: 10.1261/rna.080776.125

Ali Salman, Mikhail Loev, Tatiana Egorova, Alexey Shuvalov, Anastasia Zharikova, Sergey E Dmitriev, Ekaterina Shuvalova, Nikita Biziaev, Elena Alkalaeva

{"title":"Dual role of 3' UTR length in modulating translation termination efficiency.","authors":"Ali Salman, Mikhail Loev, Tatiana Egorova, Alexey Shuvalov, Anastasia Zharikova, Sergey E Dmitriev, Ekaterina Shuvalova, Nikita Biziaev, Elena Alkalaeva","doi":"10.1261/rna.080776.125","DOIUrl":"10.1261/rna.080776.125","url":null,"abstract":"The 3' untranslated region of mRNAs is involved in posttranscriptional control, influencing mRNA stability, localization, and translation efficiency through its interaction with various proteins and RNAs. While eukaryotic 3' UTRs are typically several hundred nucleotides long, certain protozoan species possess remarkably short 3' UTRs and have evolved alternative genetic codes where canonical stop codons are reassigned to sense codons. This suggests a potential link between 3' UTR architecture and the efficiency of translation termination. In this study, we investigate how the length and secondary structure of the 3' UTR modulate translation termination efficiency across different species. We demonstrate that shortening of 3' UTRs confers a translational advantage for mRNAs bearing UAA stop codons. Using purified pretermination complexes, we show that 3' UTR secondary structures enhance the termination rate by facilitating the spatial proximity of PABP, bound to the poly(A) tail, to eRF3a on the ribosome. Furthermore, we found that the termination rate at UGA stop codons is highly sensitive to 3' UTR length when assayed with both human and ciliate release factors. Our investigation of stop codon reassignment underscores the primary role of release factor recognition efficiency in this process. Collectively, our findings reveal that 3' UTR length and structure create a regulatory balance: While an extended 3' UTR region can hinder termination at the UGA stop codon, a structured 3' UTR facilitates the interaction between eRF3a and PABP, which promotes efficient release factor recruitment. This work establishes 3' UTR length as a key cis-regulatory factor fine-tuning the fundamental process of translation termination.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1129-1146"},"PeriodicalIF":4.3,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779722","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

The impact of read depth and read length on RNA-seq splicing analysis. 阅读深度和阅读长度对RNA-seq剪接分析的影响。

IF 4.3 3区生物学

RNA Pub Date : 2026-06-16 DOI: 10.1261/rna.080915.125

Annika Ladwig, Melina Klostermann, Kathi Zarnack

引用次数: 0

Chronology of tRNA structural dynamics prior to and during interaction with a pseudouridine synthase. 在与假尿嘧啶合酶相互作用之前和期间的tRNA结构动力学年表。

IF 4.3 3区生物学

RNA Pub Date : 2026-06-16 DOI: 10.1261/rna.080869.125

Emily M Dennis, Nico E Conoan Nieves, Madison Kadrmas, Abigail L Vaaler, Margaret L Barry, David M Garcia, Julia R Widom

{"title":"Chronology of tRNA structural dynamics prior to and during interaction with a pseudouridine synthase.","authors":"Emily M Dennis, Nico E Conoan Nieves, Madison Kadrmas, Abigail L Vaaler, Margaret L Barry, David M Garcia, Julia R Widom","doi":"10.1261/rna.080869.125","DOIUrl":"10.1261/rna.080869.125","url":null,"abstract":"Transfer RNA has long served as an exemplar of a thermodynamically stable, structured RNA. Yet, it undergoes significant structural changes upon binding and catalysis by diverse modification enzymes. We leveraged optical binding assays and single-molecule FRET to observe the structural dynamics of two yeast tRNAs, in isolation, and upon interaction with the conserved pseudouridine synthase Pus4/TruB. We show that unmodified and pseudouridylated tRNAeMet(CAU) and tRNAThr(AGU) all sample open, compact, and intermediate conformations, though tRNAThr(AGU) exhibits faster dynamics. Consistent with its role in modifying RNAs with different structural properties, Pus4 binds robustly to unmodified tRNA, tRNA that was pseudouridylated prior to engaging Pus4 (\"premodified\"), and even an unrelated riboswitch RNA. Pus4 binding to tRNAeMet(CAU) leads to additional tRNA conformational states. The ensemble of conformations explored by Pus4-bound premodified tRNA resolved within minutes back into open, compact, and intermediate states. tRNAeMet(CAU) that is initially unmodified more gradually approached the ensemble of structures that were attained rapidly by premodified tRNA. Thus, Pus4 both catalyzes a lasting chemical change on tRNA and remodels it over time after catalysis, perhaps to promote subsequent steps of tRNA maturation.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1041-1060"},"PeriodicalIF":4.3,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13270999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147594404","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

Both neighboring codon adjacent nucleotides and codon optimality influence mRNA decay rates. 邻近密码子邻近核苷酸和密码子最优性都影响mRNA的衰变速率。

IF 4.3 3区生物学

RNA Pub Date : 2026-06-16 DOI: 10.1261/rna.080900.125

Reed S Sorenson, Leslie E Sieburth

{"title":"Both neighboring codon adjacent nucleotides and codon optimality influence mRNA decay rates.","authors":"Reed S Sorenson, Leslie E Sieburth","doi":"10.1261/rna.080900.125","DOIUrl":"10.1261/rna.080900.125","url":null,"abstract":"Codon-optimality-mediated decay (COMD) is a major pathway that determines mRNA decay rates in eukaryotes. Conservation of this pathway in plants has not been demonstrated. To identify codons that might influence cotranslational mRNA decay rates, we compared codon usage bias in Arabidopsis seedling-expressed mRNAs with their mRNA half-lives (t 1/2s). Finding differences in codon usage between transcripts with short and long t 1/2s led to a model of mRNA decay rate based on codon frequencies. This codon-decay rate model explained 21% of decay rate variance in Arabidopsis and was predictive of decay rates of synonymously recoded genes. In the COMD pathway, NOT3, a component of the CCR4-NOT deadenylation complex, can detect slow ribosome decoding and trigger decay cotranslationally. Because the N-terminal sensor domain of NOT3 is retained in plant genomes, it is likely that plants, yeast, and humans use the same mechanism. However, codon optimality in Arabidopsis was not reading-frame dependent, suggesting that additional sequence features also contributed to decay rates. These features were computationally identified as specific adjacent nucleotides of neighboring codons. The influence of adjacent codons appears to be a conserved feature of cotranslational decay, as published data sets from wheat (Triticum aestivum) and fission yeast (Schizosaccharomyces pombe) also showed neighboring codon adjacent nucleotides to impact RNA decay rates. These findings show that codon sequence can influence mRNA decay rates independently of charged tRNA concentrations and suggest a paradigm of selection among synonymous codons that are decoded through wobble base-pairing.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1061-1076"},"PeriodicalIF":4.3,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676345","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

Target-site dynamics explain a large share of apparent microRNA differential expression. 靶点动力学解释了明显MicroRNA差异表达的很大一部分。

IF 4.3 3区生物学

RNA Pub Date : 2026-06-16 DOI: 10.1261/rna.080990.126

Mert Cihan, Piyush More, Maximilian Sprang, Federico Marini, Miguel A Andrade-Navarro

{"title":"Target-site dynamics explain a large share of apparent microRNA differential expression.","authors":"Mert Cihan, Piyush More, Maximilian Sprang, Federico Marini, Miguel A Andrade-Navarro","doi":"10.1261/rna.080990.126","DOIUrl":"10.1261/rna.080990.126","url":null,"abstract":"MicroRNA (miRNA) abundance reflects a dynamic balance between biogenesis, target engagement, and decay, yet differential expression analyses typically ignore changes in target-site availability driven by alternative polyadenylation (APA). We introduce MIRNAPEX, an expression-stratification-based machine learning framework that quantifies miRNA regulatory effect sizes from RNA-seq data by integrating target-gene expression with 3'UTR isoform usage to infer effective binding-site dosage. Using pan-cancer training sets, we train models that learn relationships between transcriptomic features and miRNA log fold changes, with APA patterns providing context-dependent complementary information alongside gene expression. When applied to knockdowns of core APA regulators, MIRNAPEX captured widespread 3'UTR shortening and predicted miRNA-specific shifts whose direction was consistent with changes in the APA-associated 3'UTR landscapes of target genes. Analysis of target-directed miRNA degradation interactions further showed that loss of distal decay-trigger sites coincides with increased miRNA abundance, consistent with reduced target-directed miRNA degradation. Together, these findings suggest that apparent miRNA differential expression can be associated with dynamic target-site landscapes in addition to altered miRNA transcription, and that neglecting this dimension can lead to misestimation of regulatory effect sizes.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1005-1019"},"PeriodicalIF":4.3,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13270998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779691","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

Neuronal subtype-specific ribosomal protein mRNA expression. 神经元亚型特异性核糖体蛋白mRNA表达。

IF 4.3 3区生物学

RNA Pub Date : 2026-06-16 DOI: 10.1261/rna.080954.126

Joaquín Garat, Sofía Niño-Rivero, Patricia Lagos, Andrés Di Paolo, Pablo Smircich, José Sotelo-Silveira

{"title":"Neuronal subtype-specific ribosomal protein mRNA expression.","authors":"Joaquín Garat, Sofía Niño-Rivero, Patricia Lagos, Andrés Di Paolo, Pablo Smircich, José Sotelo-Silveira","doi":"10.1261/rna.080954.126","DOIUrl":"10.1261/rna.080954.126","url":null,"abstract":"Current understanding recognizes that ribosomal proteins (RPs) have regulatory roles beyond their canonical structural functions in translation, raising the question of how their expression is organized across cell types. Given the diversity of neuronal cell types, understanding RP gene expression at the neuronal subtype level is an important and previously inaccessible question. Here, leveraging advances in single-cell transcriptomics, we analyzed single-cell RNA-seq data sets from the mouse cerebral cortex and hippocampus to examine RP mRNA expression across neuronal subtypes. We observed distinct RP mRNA expression profiles between excitatory and inhibitory neurons and found that higher Rps27 transcript levels in inhibitory neurons corresponded to increased RPS27 protein abundance. Beyond excitatory-inhibitory differences, RP mRNA expression further segregated across well-defined neuronal subclasses, with 59 of 84 RP genes differentially expressed, including enrichment of Rpl21 in Lamp5 and Rps27 in Vip interneurons. These patterns were consistent across cortical regions and reproducible across two independent single-cell technologies (Smart-seq2 and 10x Genomics). Analysis of aging- and stress-associated data sets revealed stable RP expression signatures, with limited phenotype-linked changes. Together, we present a comprehensive atlas of ribosomal protein gene expression at neuronal subclass resolution, revealing robust subclass-specific transcriptional signatures, suggesting an underestimated regulatory layer.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1077-1100"},"PeriodicalIF":4.3,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13271003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646351","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

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