RNA最新文献_第3页

NUCLEAR RNA-BINDING PROTEINS MEET CYTOPLASMIC VIRUSES. 核 RNA 结合蛋白与细胞质病毒相遇。

IF 4.2 3区生物学

RNA Pub Date : 2025-01-13 DOI: 10.1261/rna.080313.124

Alfredo Castello, Wael Kamel

引用次数: 0

rRFtargetDB: a database of Ago1-mediated targets of ribosomal RNA fragments. rRFtargetDB: ago1介导的核糖体RNA片段靶点数据库。

IF 4.2 3区生物学

RNA Pub Date : 2025-01-09 DOI: 10.1261/rna.080285.124

Lingyu Guan, Sathyanarayanan Vaidhyanathan, Andrey Grigoriev

{"title":"rRFtargetDB: a database of Ago1-mediated targets of ribosomal RNA fragments.","authors":"Lingyu Guan, Sathyanarayanan Vaidhyanathan, Andrey Grigoriev","doi":"10.1261/rna.080285.124","DOIUrl":"https://doi.org/10.1261/rna.080285.124","url":null,"abstract":"rRNA-derived fragments (rRFs) are a class of emerging post-transcriptional regulators of gene expression likely binding to the transcripts of target genes. However, the lack of knowledge about such targets hinders our understanding of rRF functions or binding mechanisms. The paucity of resources supporting the identification of the targets of rRFs creates a bottleneck in the fast-developing field. We have previously analyzed chimeric reads in crosslinked Argonaute1-RNA complexes to help infer the guide-target pairs and binding mechanisms of multiple rRFs based on experimental data in human HEK293 cells. To efficiently disseminate these results to the research community, we designed a web-based database rRFtargetDB that preserves most of the experimental results after removal of noise and has a user-friendly interface with flexible query options and filters allowing users to obtain comprehensive information on rRFs (or targets) of interest. rRFtargetDB is populated by ~163,000 experimentally determined unique rRF-mRNA pairs (~60,000 supported by ≥2 reads). Almost 30,000 rRF isoforms produced >385 000 (>156 000 with ≥2 reads) chimeras with all types of RNA targets (mRNAs and non-coding RNAs). Further analyses suggested hypothetical modes of interactions, supported by secondary structures of potential guide-target hybrids and binding motifs, essential for understanding the targeting mechanisms of rRFs. All these results (ranging from the weakest to the strongest experimental support) are presented in rRFtargetDB, whose goal is to provide a resource for building users' hypotheses on potential roles of rRFs. Further, we illustrate the value/application of the database on several examples. rRFtargetDB is freely accessible at https://grigoriev-lab.camden.rutgers.edu/tardb.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954240","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 sensing at the crossroads of autoimmunity and autoinflammation. 自身免疫和自身炎症十字路口的RNA传感。

IF 4.2 3区生物学

RNA Pub Date : 2025-01-08 DOI: 10.1261/rna.080304.124

Sandra G Williams, Soyeong Sim, Sandra L Wolin

引用次数: 0

Live-cell imaging of circular and long non-coding RNAs associated to FUS pathological aggregates by Pepper fluorescent RNA. 辣椒荧光RNA对与FUS病理聚集体相关的环状和长链非编码RNA的活细胞成像。

IF 4.2 3区生物学

RNA Pub Date : 2025-01-08 DOI: 10.1261/rna.080119.124

Erika Vitiello, Francesco Castagnetti, Lorenzo Stufera Mecarelli, Eleonora D'Ambra, Paolo Tollis, Giancarlo Ruocco, Pietro Laneve, Elisa Caffarelli, Davide Mariani, Irene Bozzoni

{"title":"Live-cell imaging of circular and long non-coding RNAs associated to FUS pathological aggregates by Pepper fluorescent RNA.","authors":"Erika Vitiello, Francesco Castagnetti, Lorenzo Stufera Mecarelli, Eleonora D'Ambra, Paolo Tollis, Giancarlo Ruocco, Pietro Laneve, Elisa Caffarelli, Davide Mariani, Irene Bozzoni","doi":"10.1261/rna.080119.124","DOIUrl":"https://doi.org/10.1261/rna.080119.124","url":null,"abstract":"Lately, important advancements in visualizing RNAs in fixed and live cells have been achieved. While mRNA imaging techniques are well-established, the development of effective methods for studying non-coding RNAs (ncRNAs) in living cells are still challenging but necessary, as they show a variety of functions and intracellular localizations, including participation in highly dynamic processes like phase-transition, which is still poorly studied in vivo. Addressing this issue, we tagged two exemplary ncRNAs with the fluorescent RNA (fRNA) Pepper. Specifically, we showed that circ-HDGFRP3 interacts with p-bodies and is recruited in pathological FUS aggregates in a dynamic fashion, and we super-resolved its distribution in such condensates via Structured Illumination Microscopy. Moreover, we tracked the long non-coding RNA (lncRNA) nHOTAIRM1, a motor neuron-specific constituent of stress granules (SG), monitoring its behavior throughout the oxidative-stress response in physiological and pathological conditions. Overall, as fRNA development progresses, our work demonstrates an effective use of Pepper for monitoring complex processes, such as phase transition, in living cells through the visualization of circular RNAs (circRNAs) and lncRNAs with super-resolution power.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954236","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

Alternative splicing factors and cardiac disease: more than just mis-splicing? 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 : 2025-01-07 DOI: 10.1261/rna.080332.124

Zachery R Gregorich, Wei Guo

{"title":"Alternative splicing factors and cardiac disease: more than just mis-splicing?","authors":"Zachery R Gregorich, Wei Guo","doi":"10.1261/rna.080332.124","DOIUrl":"https://doi.org/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 mis-splicing. 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 non-splicing 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 non-splicing 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 mis-splicing.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 : 2025-01-07 DOI: 10.1261/rna.080368.124

Pedro Bak-Gordon, James L Manley

引用次数: 0

Global analysis by LC-MS/MS of N6-methyladenosine and inosine in mRNA reveal complex incidence. 通过LC-MS/MS对mRNA中的n6 -甲基腺苷和肌苷进行全局分析，揭示了复杂的发生率。

IF 4.2 3区生物学

RNA Pub Date : 2025-01-02 DOI: 10.1261/rna.080324.124

Stanislav Stejskal, Veronika Rajecka, Helena Covelo-Molares, Ketty Sinigaglia, Kvetoslava Brozinova, Linda Kasiarova, Michaela Dohnalkova, Paul Eduardo Reyes-Gutierrez, Hana Cahova, Liam Peter Keegan, Mary A O'Connell, Stepanka Vanacova

{"title":"Global analysis by LC-MS/MS of N6-methyladenosine and inosine in mRNA reveal complex incidence.","authors":"Stanislav Stejskal, Veronika Rajecka, Helena Covelo-Molares, Ketty Sinigaglia, Kvetoslava Brozinova, Linda Kasiarova, Michaela Dohnalkova, Paul Eduardo Reyes-Gutierrez, Hana Cahova, Liam Peter Keegan, Mary A O'Connell, Stepanka Vanacova","doi":"10.1261/rna.080324.124","DOIUrl":"https://doi.org/10.1261/rna.080324.124","url":null,"abstract":"The precise and unambiguous detection and quantification of internal RNA modifications represents a critical step for understanding their physiological functions. The methods of direct RNA sequencing are quickly developing allowing for the precise location of internal RNA marks. This detection is however not quantitative and still presents detection limits. One of the biggest remaining challenges in the field is still the detection and quantification of m6A, m6Am, inosine and m1A modifications of adenosine. The second intriguing and timely question remaining to be addressed is the extent to which individual marks are coregulated or potentially can affect each other. Here we present a methodological approach to detect and quantify several key mRNA modifications in human total RNA and in mRNA, which is difficult to purify way from contaminating tRNA. We show that the adenosine demethylase FTO primarily targets m6Am marks in noncoding RNAs in HEK293T cells. Surprisingly, we observe little effect of FTO or ALKBH5 depletion on the m6A mRNA levels. Interestingly, upregulation of ALKBH5 is accompanied by an increase in inosine level in overall mRNA.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922795","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 editing in disease: mechanisms and therapeutic potential. 疾病中的RNA编辑：机制和治疗潜力。

IF 4.2 3区生物学

RNA Pub Date : 2025-01-02 DOI: 10.1261/rna.080331.124

Kasra Honarmand Tamizkar, Michael F Jantsch

{"title":"RNA editing in disease: mechanisms and therapeutic potential.","authors":"Kasra Honarmand Tamizkar, Michael F Jantsch","doi":"10.1261/rna.080331.124","DOIUrl":"https://doi.org/10.1261/rna.080331.124","url":null,"abstract":"Adenosine to inosine conversion by ADARs was first identified in the late eighties of the previous century. As the conversion of adenosines to inosines can be easily detected by sequencing of cDNAs, where the presence of an inosine reads out as a guanosine, the analysis of this type of RNA-editing has become widespread. Consequently, several pipelines for detecting inosines in transcriptomes have become available. Still, how to interpret the consequences and alterations of editomes is a matter of debate. In particular, the cause or consequence of altered editomes on disease development is poorly understood. Similarly, absolute frequencies of editing events in single molecules, their longitudinal distribution, and naturally occurring changes during development, in different tissues, or in response to physiological changes need to be explored. Lastly, while the use of site-directed RNA-editing as a treatment of certain genetic diseases is rapidly evolving, the applicability of this technology still faces several technical obstacles. In this review, we describe the current state of knowledge on adenosine deamination-type RNA-editing, its involvement in disease development, and its potential as a therapeutic. Lastly, we highlight open challenges and questions that need to be addressed.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922796","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

Thermodynamic control of mismatch discrimination for extensive splicing regulation of PKM pre-mRNA. PKM前体mrna广泛剪接调控错配辨别的热力学控制。

IF 4.2 3区生物学

RNA Pub Date : 2024-12-30 DOI: 10.1261/rna.080212.124

Natalia Bartys, Jolanta Lisowiec-Wachnicka, Anna Pasternak

{"title":"Thermodynamic control of mismatch discrimination for extensive splicing regulation of PKM pre-mRNA.","authors":"Natalia Bartys, Jolanta Lisowiec-Wachnicka, Anna Pasternak","doi":"10.1261/rna.080212.124","DOIUrl":"https://doi.org/10.1261/rna.080212.124","url":null,"abstract":"In this article, we present an approach to maximizing the splicing regulatory properties of splice-switching oligonucleotide (SSO) designed to regulate alternative splicing of PKM pre-mRNA. The studied SSO interacts with the regulatory element in exon 10 of PKM pre-mRNA and contributes to a significant reduction of PKM2 level with a simultaneous increase of the PKM1 isoform. This SSO forms a duplex not only with the regulatory fragment of exon 10 but also with a similar RNA fragment of intron 9. The impact of this unspecific interaction on SSO regulatory properties, as well as the functional role of the intron 9 fragment, remains debatable. Herein, two types of modified nucleotides, unlocked nucleic acids (UNAs) and locked nucleic acids (LNAs), were used to study mismatch discrimination within duplexes involving modified SSOs. Our studies showed that LNAs increased mismatch discrimination, resulting in stronger regulatory properties of SSO. On the other hand, UNA reduced mismatch discrimination, decreasing the potentially therapeutic properties of SSO. The results indicate that specific interactions with exon 10 are more favorable for therapeutic applications, than simultaneous hybridization with intron 9 and exon 10. The results also suggest the lack of a regulatory role for the intron 9 target site in alternative splicing of PKM pre-mRNA.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966496","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 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 : 2024-12-26 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 non-coding genes.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0