RNA最新文献_第4页

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

Trinucleotide Repeat Expansion and RNA Dysregulation in Fragile X Syndrome: Emerging Therapeutic Approaches. 脆性X综合征中的三核苷酸重复扩增和RNA失调：新兴的治疗方法。

IF 4.2 3区生物学

RNA Pub Date : 2024-12-26 DOI: 10.1261/rna.080270.124

Suna Jung, Joel D Richter

{"title":"Trinucleotide Repeat Expansion and RNA Dysregulation in Fragile X Syndrome: Emerging Therapeutic Approaches.","authors":"Suna Jung, Joel D Richter","doi":"10.1261/rna.080270.124","DOIUrl":"10.1261/rna.080270.124","url":null,"abstract":"Fragile X Syndrome (FXS) is characterized by intellectual impairment caused by CGG repeat expansion in the FMR1 gene. When repeats exceed 200, they induce DNA methylation of the promoter and the repeat region, resulting in transcriptional silencing of the FMR1 gene and the subsequent loss of FMRP protein. In the past decade or so, research has focused on the role of FMRP as an RNA-binding protein involved in translation inhibition in the brain in FXS model mice, particularly by slowing or stalling ribosome translocation on mRNA. More recent advances have shown that FMRP has a profound role in RNA splicing, at least in some cases by modulating the translation of splicing factor mRNAs. In a surprise, the human FMR1 gene is transcribed in most cases even with a full CGG expansion. However, much of the FMR1 that is produced is mis-spliced, which can be corrected by splice-switching antisense oligonucleotide (ASO) administration. Other recent findings suggest that inhibition of multiple kinases can demethylate the FMR1 gene and induce the formation of an R-loop in the CGG repeat region, leading to contraction of the repeat and FMRP restoration. These insights are paving the way for possible future therapeutic approaches for this disorder. We highlight the importance of FMRP restoration by ASO-mediated splice switching or CGG repeat modulation as key advances that may lead to successful treatments for FXS.","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":"142897134","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

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 : 2024-12-24 DOI: 10.1261/rna.080257.124

Takeshi Chujo, Kazuhito Tomizawa

引用次数: 0

N6-methyladenosine reader YTHDF2 in cell state transition and antitumor immunity. n6 -甲基腺苷解读器YTHDF2在细胞状态转换和抗肿瘤免疫中的作用。

IF 4.2 3区生物学

RNA Pub Date : 2024-12-24 DOI: 10.1261/rna.080259.124

Liangliang Wang, Ralph R Weichselbaum, Chuan He

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 : 2024-12-23 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

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 : 2024-12-18 DOI: 10.1261/rna.080353.124

Gideon Dreyfuss

引用次数: 0

An internal loop region is responsible for inherent target specificity of bacterial cold-shock proteins. 细菌冷休克蛋白的固有目标特异性是由一个内环区域造成的。

IF 4.2 3区生物学

RNA Pub Date : 2024-12-16 DOI: 10.1261/rna.080163.124

Satoshi Hasegawa, Rerina Inose, Mizuki Igarashi, Megumi Tsurumaki, Motofumi Saito, Tatsuo Yanagisawa, Akio Kanai, Teppei Morita

{"title":"An internal loop region is responsible for inherent target specificity of bacterial cold-shock proteins.","authors":"Satoshi Hasegawa, Rerina Inose, Mizuki Igarashi, Megumi Tsurumaki, Motofumi Saito, Tatsuo Yanagisawa, Akio Kanai, Teppei Morita","doi":"10.1261/rna.080163.124","DOIUrl":"10.1261/rna.080163.124","url":null,"abstract":"Cold-shock proteins (Csps), of around 70 amino acids, share a protein fold for the cold-shock domain (CSD) that contains RNA-binding motifs, RNP1 and RNP2, and constitute one family of bacterial RNA-binding proteins. Despite similar amino acid composition, Csps have been shown to individually possess inherent specific functions. Here, we identify the molecular differences in Csps that allow selective recognition of RNA targets. Using chimeras and mutants of Escherichia coli CspD and CspA, we demonstrate that Lys43-Ala44 in an internal loop of CspD, and the N-terminal portion with Lys4 of CspA, are important for determining their target specificities. Pull-down assays suggest that these distinct specificities reflect differences in the ability to act on the target RNAs rather than differences in binding to the RNA targets. A phylogenetic tree constructed from 1,573 Csps reveals that the Csps containing Lys-Ala in the loop form a monophyletic clade, and the members in this clade are shown to have target specificities similar to E. coli CspD. The phylogenetic tree also finds a small cluster of Csps containing Lys-Glu in the loop, and these exhibit a different specificity than E. coli CspD. Examination of this difference suggests a role of the loop of CspD-type proteins in recognition of specific targets. Additionally, each identified type of Csp shows a different distribution pattern among bacteria. Our findings provide a basis for subclassification of Csps based on target RNA specificity, which will be useful for understanding the functional specialization of Csps.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"67-85"},"PeriodicalIF":4.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473665","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 bioconjugate-based delivery systems for nucleic acids. 开发基于生物共轭物的核酸输送系统。

IF 4.2 3区生物学

RNA Pub Date : 2024-12-16 DOI: 10.1261/rna.080273.124

Aniket Wahane, Vishal Kasina, Mounika Pathuri, Ciara Marro-Wilson, Anisha Gupta, Frank J Slack, Raman Bahal

{"title":"Development of bioconjugate-based delivery systems for nucleic acids.","authors":"Aniket Wahane, Vishal Kasina, Mounika Pathuri, Ciara Marro-Wilson, Anisha Gupta, Frank J Slack, Raman Bahal","doi":"10.1261/rna.080273.124","DOIUrl":"10.1261/rna.080273.124","url":null,"abstract":"Nucleic acids are a class of drugs that can modulate gene and protein expression by various mechanisms, namely, RNAi, mRNA degradation by RNase H cleavage, splice modulation, and steric blocking of protein binding or mRNA translation, thus exhibiting immense potential to treat various genetic and rare diseases. Unlike protein-targeted therapeutics, the clinical use of nucleic acids relies on Watson-Crick sequence recognition to regulate aberrant gene expression and impede protein translation. Though promising, targeted delivery remains a bottleneck for the clinical adoption of nucleic acid-based therapeutics. To overcome the delivery challenges associated with nucleic acids, various chemical modifications and bioconjugation-based delivery strategies have been explored. Currently, liver targeting by N-acetyl galactosamine (GalNAc) conjugation has been at the forefront for the treatment of rare and various metabolic diseases, which has led to FDA approval of four nucleic acid drugs. In addition, various other bioconjugation strategies have been explored to facilitate active organ and cell-enriched targeting. This review briefly covers the different classes of nucleic acids, their mechanisms of action, and their challenges. We also elaborate on recent advances in bioconjugation strategies in developing a diverse set of ligands for targeted delivery of nucleic acid drugs.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1-13"},"PeriodicalIF":4.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547091","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 oligonucleotides containing N7-regioisomer of guanosine: influence on thermodynamic properties and structure of RNA duplexes. 含有鸟苷 N7-regioisomer 的寡核苷酸。对 RNA 双链体热力学性质和结构的影响。

IF 4.2 3区生物学

RNA Pub Date : 2024-12-16 DOI: 10.1261/rna.080106.124

Aleksandra Jarmolowicz, Nivedita Dutta, Witold Andralojc, Joanna Sarzynska, Grzegorz Framski, Daniel Baranowski, Jerzy Boryski, Ansuman Lahiri, Zofia Gdaniec, Elzbieta Kierzek, Ryszard Kierzek

{"title":"The oligonucleotides containing N7-regioisomer of guanosine: influence on thermodynamic properties and structure of RNA duplexes.","authors":"Aleksandra Jarmolowicz, Nivedita Dutta, Witold Andralojc, Joanna Sarzynska, Grzegorz Framski, Daniel Baranowski, Jerzy Boryski, Ansuman Lahiri, Zofia Gdaniec, Elzbieta Kierzek, Ryszard Kierzek","doi":"10.1261/rna.080106.124","DOIUrl":"10.1261/rna.080106.124","url":null,"abstract":"During the chemical synthesis of the purine riboside, N7-regioisomer is kinetically formed, whereas N9-regioisomer is a thermodynamically formed product. We have studied the effect of substituting N9-regioisomer of guanosine with its N7-regioisomer (N7-guanosine, 7G) at a central position of several RNA duplexes. We found that this single substitution by 7G severely diminished their thermodynamic stabilities when 7G paired with C and U, but remarkably, led to a significant amount of stabilization in most of the duplexes when forming mismatches with G and A. The extent of stabilization was observed to be dependent on the sequence and orientation of neighboring base pairs of N7-guanosine. 1D and 2D NMR studies on the duplexes along with extensive molecular dynamics simulations revealed the conformational differences occurring due to the substitution of G by 7G, and it was observed that the thermodynamic results were largely explainable by considering the formation of stable noncanonical hydrogen bonding interactions, although other interactions such as stacking and electrostatic interactions could also play a role. These observations can have important applications in the design of RNA-based disease diagnostics and therapeutics.","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"86-99"},"PeriodicalIF":4.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522880","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

Conserved role for spliceosomal component PRPF40A in microexon splicing. 剪接体成分 PRPF40A 在微外显子剪接中的保守作用

IF 4.2 3区生物学

RNA Pub Date : 2024-12-16 DOI: 10.1261/rna.080142.124

Bikash Choudhary, Adam Norris

引用次数: 0