IF 4.2 3区生物学

RNA Pub Date : 2025-02-28 DOI: 10.1261/rna.080274.124

Susmit Narayan Chaudhury, Erdong Ding, Nathan Edward Jespersen, Jose N Onuchic, Karissa Y Sanbonmatsu

{"title":"Conformational heterogeneity in the dGsw purine riboswitch: role of Mg²⁺ and 2'-dG in aptamer folding.","authors":"Susmit Narayan Chaudhury, Erdong Ding, Nathan Edward Jespersen, Jose N Onuchic, Karissa Y Sanbonmatsu","doi":"10.1261/rna.080274.124","DOIUrl":"https://doi.org/10.1261/rna.080274.124","url":null,"abstract":"Recent advancements in RNA structural biology have focused on unraveling the complexities of non-coding mRNA elements like riboswitches. These cis-acting regulatory regions undergo structural changes in response to specific cellular metabolites, leading to up or downregulation of downstream genes. The purine riboswitch family regulates many prokaryotic genes involved in purine degradation and biosynthesis. They feature an aptamer domain organized around a 3-way helical junction, where ligand encapsulation occurs at the junctional core. In our study, we chemically probed the aptamer domain of the 2'-dG-sensing purine riboswitch from Mesoplasma florum (dGsw) under various solution conditions to understand how Mg²⁺ and 2'-dG influence riboswitch folding. Here, we find that efficient 2'-dG binding strongly depends on Mg²⁺, indicating that Mg²⁺ is essential for priming dGsw for ligand interactions. We identified a previously undescribed sequence in the 5' tail of dGsw that is complementary to a conserved helix. The inclusion of this region in a construct led to intramolecular competition between the alternate helix, Palt, and P1. Mutational analysis confirmed that 5' flanking end of the aptamer domain forms an alternate helix in the absence of ligand. Molecular dynamics simulations revealed that this alternative conformation is stable. This helix may, therefore, facilitate the formation of an anti-terminator helix by opening the 3-way junction surrounding the 2'-dG binding site. Our study further establishes the importance of a closed terminal P1 helix conformation for metabolite binding and suggests that the delicate interplay between P1 and Palt may fine-tune downstream gene regulation. These insights offer a new perspective on riboswitch structure and enhance our understanding of the role that a conformational ensemble plays in riboswitch activity and regulation.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531459","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 PUF RNA-binding protein, FBF-2, maintains stem cells without binding to RNA.

IF 4.2 3区生物学

RNA Pub Date : 2025-02-21 DOI: 10.1261/rna.080307.124

Brian H Carrick, Sarah L Crittenden, MaryGrace Linsley, Stephany J Costa Dos Santos, Marvin Wickens, Judith Kimble

引用次数: 0

Alternative splicing factors and cardiac disease: more than just missplicing? 选择性剪接因子与心脏病：不仅仅是剪接错误？

IF 4.2 3区生物学

RNA Pub Date : 2025-02-19 DOI: 10.1261/rna.080332.124

Zachery R Gregorich, Wei Guo

{"title":"Alternative splicing factors and cardiac disease: more than just missplicing?","authors":"Zachery R Gregorich, Wei Guo","doi":"10.1261/rna.080332.124","DOIUrl":"10.1261/rna.080332.124","url":null,"abstract":"Alternative splicing (AS) is the process wherein the exons from a single gene are joined in different combinations to produce nonidentical, albeit related, RNA transcripts. This process is important for the development and physiological function of many organs and is particularly important in the heart. Notably, AS has been implicated in cardiac disease and failure, and a growing number of genetic variants in AS factors have been identified in association with cardiac malformation and/or disease. With the field poised to interrogate how these variants affect cardiac development and disease, an understandable point of emphasis will undoubtedly be on downstream target gene missplicing. In this Perspective article, we would like to encourage consideration not only of the potential for novel disease mechanisms, but also for contributions from disruption of the ever-expanding list of nonsplicing functions ascribed to many AS factors. We discuss the emergence of a novel cardiac disease mechanism based on pathogenic RNA granules and speculate on the generality of such a mechanism among localization-disrupting AS factor genetic variants. We also highlight emerging nonsplicing functions attributed to several AS factors with cardiac disease-associated genetic variants in the hopes of pointing to avenues for exploration of mechanisms that may contribute to disease alongside target gene missplicing.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"300-306"},"PeriodicalIF":4.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954234","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

SF3B1: from core splicing factor to oncogenic driver. SF3B1：从核心剪接因子到致癌驱动因子。

IF 4.2 3区生物学

RNA Pub Date : 2025-02-19 DOI: 10.1261/rna.080368.124

Pedro Bak-Gordon, James L Manley

引用次数: 0

RNA gain-of-function mechanisms in short tandem repeat diseases. 短串联重复疾病中的RNA功能获得机制。

IF 4.2 3区生物学

RNA Pub Date : 2025-02-19 DOI: 10.1261/rna.080277.124

Mackenzie L Davenport, Maurice S Swanson

{"title":"RNA gain-of-function mechanisms in short tandem repeat diseases.","authors":"Mackenzie L Davenport, Maurice S Swanson","doi":"10.1261/rna.080277.124","DOIUrl":"10.1261/rna.080277.124","url":null,"abstract":"As adaptors, catalysts, guides, messengers, scaffolds, and structural components, RNAs perform an impressive array of cellular regulatory functions often by recruiting RNA-binding proteins (RBPs) to form ribonucleoprotein complexes (RNPs). While this RNA-RBP interaction network allows precise RNP assembly and the subsequent structural dynamics required for normal functions, RNA motif mutations may trigger the formation of aberrant RNP structures that lead to cell dysfunction and disease. Here, we provide our perspective on one type of RNA motif mutation, RNA gain-of-function mutations associated with the abnormal expansion of short tandem repeats (STRs) that underlie multiple developmental and degenerative diseases. We first discuss our current understanding of normal polymorphic STR functions in RNA processing and localization followed by an assessment of the pathogenic roles of STR expansions in the neuromuscular disease myotonic dystrophy. We also highlight ongoing questions and controversies focused on STR-based insights into the regulation of nuclear RNA processing and export as well as the relevance of the RNA gain-of-function pathomechanism for other STR expansion disorders in both coding and noncoding genes.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"349-358"},"PeriodicalIF":4.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897132","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 unfolding landscape of RNA and disease.

IF 4.2 3区生物学

RNA Pub Date : 2025-02-19 DOI: 10.1261/rna.080382.125

Maria Carmo-Fonseca, Juan Valcárcel

引用次数: 0

Mitochondrial tRNA modifications: functions, diseases caused by their loss, and treatment strategies. 线粒体tRNA修饰：功能，由其丢失引起的疾病，以及治疗策略。

IF 4.2 3区生物学

RNA Pub Date : 2025-02-19 DOI: 10.1261/rna.080257.124

Takeshi Chujo, Kazuhito Tomizawa

引用次数: 0

RNA-binding proteins in disease etiology: fragile X syndrome and spinal muscular atrophy. 疾病病因学中的rna结合蛋白：脆性X综合征和脊髓性肌萎缩症。

IF 4.2 3区生物学

RNA Pub Date : 2025-02-19 DOI: 10.1261/rna.080353.124

Gideon Dreyfuss

引用次数: 0

A general and biomedical perspective of viral quasispecies. 病毒准种的一般和生物医学观点。

IF 4.2 3区生物学

RNA Pub Date : 2025-02-19 DOI: 10.1261/rna.080280.124

Esteban Domingo, Brenda Martínez-González, Pilar Somovilla, Carlos García-Crespo, María Eugenia Soria, Ana Isabel de Ávila, Ignacio Gadea, Celia Perales

{"title":"A general and biomedical perspective of viral quasispecies.","authors":"Esteban Domingo, Brenda Martínez-González, Pilar Somovilla, Carlos García-Crespo, María Eugenia Soria, Ana Isabel de Ávila, Ignacio Gadea, Celia Perales","doi":"10.1261/rna.080280.124","DOIUrl":"10.1261/rna.080280.124","url":null,"abstract":"Viral quasispecies refers to the complex and dynamic mutant distributions (also termed mutant spectra, clouds, or swarms) that arise as a result of high error rates during RNA genome replication. The mutant spectrum of individual RNA virus populations is modified by continuous generation of variant genomes, competition and interactions among them, environmental influences, bottleneck events, and bloc transmission of viral particles. Quasispecies dynamics provides a new perspective on how viruses adapt, evolve, and cause disease, and sheds light on strategies to combat them. Molecular flexibility, together with ample opportunity of mutant cloud traffic in our global world, are key ingredients of viral disease emergences, as exemplified by the recent COVID-19 pandemic. In the present article, we present a brief overview of the molecular basis of mutant swarm formation and dynamics, and how the latter relates to viral disease and epidemic spread. We outline future challenges derived of the highly diverse cellular world in which viruses are necessarily installed.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"429-443"},"PeriodicalIF":4.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847585","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

Exploring the therapeutic potential of modulating nonsense-mediated mRNA decay. 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 : 2025-02-19 DOI: 10.1261/rna.080334.124

Mary McMahon, Lynne E Maquat

引用次数: 0

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