Wiley Interdisciplinary Reviews: RNA最新文献

Splicing of pre-mRNA is an essential part of eukaryotic gene expression. Serine-/arginine-rich (SR) proteins are highly conserved RNA-binding proteins present in all metazoans and plants. SR proteins are involved in constitutive and alternative splicing, thereby regulating the transcriptome and proteome diversity in the organism. In addition to their role in splicing, SR proteins are also involved in mRNA export, nonsense-mediated mRNA decay, mRNA stability, and translation. Due to their pivotal roles in mRNA metabolism, SR proteins play essential roles in normal growth and development. Hence, any misregulation of this set of proteins causes developmental defects in both plants and animals. SR proteins from the animal kingdom are extensively studied for their canonical and noncanonical functions. Compared with the animal kingdom, plant genomes harbor more SR protein-encoding genes and greater diversity of SR proteins, which are probably evolved for plant-specific functions. Evidence from both plants and animals confirms the essential role of SR proteins as regulators of gene expression influencing cellular processes, developmental stages, and disease conditions. This article is categorized under: RNA Processing > Splicing Mechanisms RNA Processing > Splicing Regulation/Alternative Splicing.

The mammalian cleavage factor I subunit CFIm25 (NUDT21) binds to the UGUA sequences of precursor RNAs. Traditionally, CFIm25 is known to facilitate 3' end formation of pre-mRNAs resulting in the formation of polyadenylated transcripts. Recent studies suggest that CFIm25 may be involved in the cyclization and hence generation of circular RNAs (circRNAs) that contain UGUA motifs. These circRNAs act as competing endogenous RNAs (ceRNAs) that disrupt the ceRNA-miRNA-mRNA axis. Other emerging roles of CFIm25 include regulating both alternative splicing and alternative polyadenylation (APA). APA generates different sized transcripts that may code for different proteins, or more commonly transcripts that code for the same protein but differ in the length and sequence content of their 3' UTRs (3' UTR-APA). CFIm25 mediated global changes in 3' UTR-APA affect human physiology including spermatogenesis and the determination of cell fate. Deregulation of CFIm25 and changes in 3' UTR-APA have been implicated in several human diseases including cancer. In many cancers, CFIm25 acts as a tumor suppressor. However, there are some cancers where CFIm25 has the opposite effect. Alterations in CFIm25-driven 3' UTR-APA may also play a role in neural dysfunction and fibrosis. CFIm25 mediated 3' UTR-APA changes can be used to generate specific signatures that can be used as potential biomarkers in development and disease. Due to the emerging role of CFIm25 as a regulator of the aforementioned RNA processing events, modulation of CFIm25 levels may be a novel viable therapeutic approach. This article is categorized under: RNA Processing > 3' End Processing RNA in Disease and Development > RNA in Disease.

With the identification of huge amount of noncoding RNAs in recent years, the concept of RNA localization has extended from traditional mRNA export to RNA export of mRNA and ncRNA as well as nuclear retention of ncRNA. This review aims to summarize the recent findings from studies on the mechanisms of export of different RNAs and nuclear retention of some lncRNAs in higher eukaryotes, with a focus on splicing-dependent TREX recruitment for the export of spliced mRNA and the sequence-dependent mechanism of mRNA export in the absence of splicing. In addition, evidence to support the involvement of m⁶ A modification in RNA export with the coordination between the methylase complex and TREX complex as well as sequence-dependent nuclear retention of lncRNA is recapitulated. Finally, a model of sequence-dependent RNA localization is proposed along with the many questions that remain to be answered. This article is categorized under: RNA Export and Localization > RNA Localization RNA Export and Localization > Nuclear Export/Import.

Evolution and change generated an incredible diversity of organisms on this earth. Yet, some processes are so central to life that change is strongly selected against. Synthesis of the eukaryotic messenger RNA is one example. The assemblies that carry out transcription and processing (capping, polyadenylation, and splicing) are so conserved that most genes have recognizable orthologs in yeast and humans. Naturally, most would conclude transcription and processing are identical in both sexes. However, this is an assumption. Men and women vastly differ in their physiologies. The incidence of pathologies, symptom presentation, disease outcome, and therapeutic response in each sex vary enormously. Despite the harm ignorance causes women, biological research has been historically carried out without regard to sex. The male mouse was the default mammal. A cultured cell's sex was considered irrelevant. Attempts to fill this knowledge gap have revealed molecular dissimilarities. For example, the earliest embryonic male and female transcriptomes differ long before fetal sex hormones appear. We used public data to challenge the assumption of sameness by reviewing reports of sex-biased gene expression and gene targeting. We focused on 120 genes encoding nonregulatory proteins involved in mRNA synthesis. Remarkably, genes with recognizable orthologs in yeast and thus LEAST likely to differ, did differ between the sexes. The rapidly growing public databases can be used to compare the expression of any gene in male and female tissues. Appreciating the principles that drive sex differences will enrich our understanding of RNA biology in all humans-men and women. This article is categorized under: RNA in Disease and Development > RNA in Development RNA Evolution and Genomics > Computational Analyses of RNA.

Alternative splicing (AS) is a gene regulatory mechanism that plants adapt to modulate gene expression (GE) in multiple ways. AS generates alternative isoforms of the same gene following various development and environmental stimuli, increasing transcriptome plasticity and proteome complexity. AS controls the expression levels of certain genes and regulates GE networks that shape plant adaptations through nonsense-mediated decay (NMD). This review intends to discuss AS modulation, from interaction with noncoding RNAs to the established roles of splicing factors (SFs) in response to endogenous and exogenous cues. We aim to gather such studies that highlight the magnitude and impact of AS, which are not always clear from individual articles, when AS is increasing in individual genes and at a global level. This work also anticipates making plant researchers know that AS is likely to occur in their investigations and that dynamic changes in AS and their effects must be frequently considered. We also review our understanding of AS-mediated posttranscriptional modulation of plant stress tolerance and discuss its potential application in crop improvement in the future. This article is categorized under: RNA Processing > Splicing Regulation/Alternative Splicing RNA Processing > Splicing Mechanisms RNA-Based Catalysis > RNA Catalysis in Splicing and Translation.

Osteoarthritis (OA) is a frequent musculoskeletal disorder affecting millions of people worldwide. Despite advances in understanding the pathogenesis of OA, prognostic biomarkers or effective targeted treatment are not currently available. Research on epigenetic factors has yielded some new insights as new technologies for their detection continue to emerge. In this context, non-coding RNAs, including microRNAs, long non-coding RNAs, circular RNAs, piwi-interacting RNAs, and small nucleolar RNAs, regulate intracellular signaling pathways and biological processes that have a crucial role in the development of several diseases. In this review, we present current knowledge on the role of epigenetic factors with a focus on non-coding RNAs in the development, prediction and treatment of OA. This article is categorized under: RNA in Disease and Development > RNA in Disease.

Central nervous system injury diseases can cause the loss of many neurons, and it is difficult to regenerate. The field of regenerative medicine believes that supplementing the missing neurons may be an ideal method for nerve injury repair. Recent studies have found that down-regulation of polypyrimidine tract binding protein 1 (PTBP1) expression can make glial cells transdifferentiate into different types of neurons, which is expected to be an alternative therapy to restore neuronal function. This article summarized the research progress on the structure and biological function of the PTBP family, the mutual regulation of PTBP1 and PTBP2, their role in neurogenesis, and the latest research progress in targeting PTBP1 to mediate the transdifferentiation of glial cells into neurons, which may provide some new strategies and new ideas for the future treatment of central nervous system injury and neurodegenerative diseases. This article is categorized under: RNA Processing > Splicing Regulation/Alternative Splicing.

RNA helicases constitute a large family of proteins that play critical roles in mediating RNA function. They have been implicated in all facets of gene expression pathways involving RNA, from transcription to processing, transport and translation, and storage and decay. There is significant interest in developing small molecule inhibitors to RNA helicases as some family members have been documented to be dysregulated in neurological and neurodevelopment disorders, as well as in cancers. Although different functional properties of RNA helicases offer multiple opportunities for small molecule development, molecular staples have recently come to the forefront. These bifunctional molecules interact with both protein and RNA components to lock them together, thereby imparting novel gain-of-function properties to their targets. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Small Molecule-RNA Interactions RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.

Thousands of unique noncoding RNAs (ncRNAs) are expressed in human cells, some are tissue or cell type specific whereas others are considered as house-keeping molecules. Studies over the last decade have modified our perception of ncRNAs from transcriptional noise to functional regulatory transcripts that influence a variety of molecular processes such as chromatin remodeling, transcription, post-transcriptional modifications, or signal transduction. Consequently, aberrant expression of many ncRNAs plays a causative role in the initiation and progression of various diseases. Since the identification of its developmental role, the long ncRNA DNM3OS (Dynamin 3 Opposite Strand) has attracted attention of researchers in distinct fields including oncology, fibroproliferative diseases, or bone disorders. Mechanistic studies have in particular revealed the multifaceted nature of DNM3OS and its important pathogenic role in several human disorders. In this review, we summarize the current knowledge of DNM3OS functions in diseases, with an emphasis on its potential as a novel therapeutic target. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development.

An important proportion of microRNA (miRNA) genes tend to lie close to each other within animal genomes. Such genomic organization is generally referred to as miRNA clusters. Even though many miRNA clusters have been greatly studied, most attention has been usually focused on functional impacts of clustered miRNA co-expression. However, there is also another compelling aspect about these miRNA clusters, their polycistronic nature. Being transcribed on a single RNA precursor, polycistronic miRNAs benefit from common transcriptional regulation allowing their coordinated expression. And yet, numerous reports have revealed striking discrepancies in the accumulation of mature miRNAs produced from the same cluster. Indeed, the larger polycistronic transcripts can act as platforms providing unforeseen post-transcriptional regulatory mechanisms controlling individual miRNA processing, thus leading to differential miRNA expression, and sometimes even challenging the general assumption that polycistronic miRNAs are co-expressed. In this review, we aim to address the current knowledge about how miRNA polycistrons are post-transcriptionally regulated. In particular, we will focus on the mechanisms occurring at the level of the primary transcript, which are highly relevant for individual miRNA processing and as such have a direct repercussion on miRNA function within the cell. This article is categorized under: RNA Processing > Processing of Small RNAs Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.