RNA Biology最新文献

{"title":"FMRP cooperates with miRISC components to repress translation and regulate neurite morphogenesis in <i>Drosophila</i>.","authors":"Navneeta Kaul, Sarala J Pradhan, Nathan G Boin, Madeleine M Mason, Julian Rosales, Emily L Starke, Emily C Wilkinson, Erich G Chapman, Scott A Barbee","doi":"10.1080/15476286.2024.2392304","DOIUrl":"10.1080/15476286.2024.2392304","url":null,"abstract":"<p><p>Fragile X Syndrome (FXS) is the most common inherited form of intellectual disability and is caused by mutations in the gene encoding the Fragile X messenger ribonucleoprotein (FMRP). FMRP is an evolutionarily conserved and neuronally enriched RNA-binding protein (RBP) with functions in RNA editing, RNA transport, and protein translation. Specific target RNAs play critical roles in neurodevelopment, including the regulation of neurite morphogenesis, synaptic plasticity, and cognitive function. The different biological functions of FMRP are modulated by its cooperative interaction with distinct sets of neuronal RNA and protein-binding partners. Here, we focus on interactions between FMRP and components of the microRNA (miRNA) pathway. Using the <i>Drosophila</i> S2 cell model system, we show that the <i>Drosophila</i> ortholog of FMRP (dFMRP) can repress translation when directly tethered to a reporter mRNA. This repression requires the activity of AGO1, GW182, and MOV10/Armitage, conserved proteins associated with the miRNA-containing RNA-induced silencing complex (miRISC). Additionally, we find that untagged dFMRP can interact with a short stem-loop sequence in the translational reporter, a prerequisite for repression by exogenous miR-958. Finally, we demonstrate that dFmr1 interacts genetically with GW182 to control neurite morphogenesis. These data suggest that dFMRP may recruit the miRISC to nearby miRNA binding sites and repress translation via its cooperative interactions with evolutionarily conserved components of the miRNA pathway.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081388","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}

{"title":"Role of RNA polymerase III transcription and regulation in ischaemic stroke.","authors":"Chi Kwan Tsang, X F Steven Zheng","doi":"10.1080/15476286.2024.2409554","DOIUrl":"10.1080/15476286.2024.2409554","url":null,"abstract":"<p><p>Ischaemic stroke is a leading cause of death and life-long disability due to neuronal cell death resulting from interruption of glucose and oxygen supplies. RNA polymerase III (Pol III)-dependent transcription plays a central role in protein synthesis that is necessary for normal cerebral neuronal functions, and the survival and recovery under pathological conditions. Notably, Pol III transcription is highly sensitive to ischaemic stress that is known to rapidly shut down Pol III transcriptional activity. However, its precise role in ischaemic stroke, especially during the acute and recovery phases, remains poorly understood. The microenvironment within the ischaemic brain undergoes dynamic changes in different phases after stroke. Emerging evidence highlights the distinct roles of Pol III transcription in neuroprotection during the acute phase and repair during the recovery phase of stroke. Additionally, investigations into the mTOR-MAF1 signalling pathway, a conserved regulator of Pol-III transcription, reveal its therapeutic potential in enhancing acute phase neuroprotection and recovery phase repair.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372755","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}

{"title":"Truncating the spliceosomal 'rope protein' Prp45 results in Htz1 dependent phenotypes.","authors":"Kateřina Abrhámová, Martina Groušlová, Anna Valentová, Xinxin Hao, Beidong Liu, Martin Převorovský, Ondřej Gahura, František Půta, Per Sunnerhagen, Petr Folk","doi":"10.1080/15476286.2024.2348896","DOIUrl":"10.1080/15476286.2024.2348896","url":null,"abstract":"<p><p>Spliceosome assembly contributes an important but incompletely understood aspect of splicing regulation. Prp45 is a yeast splicing factor which runs as an extended fold through the spliceosome, and which may be important for bringing its components together. We performed a whole genome analysis of the genetic interaction network of the truncated allele of <i>PRP45</i> (<i>prp45</i>(1-169)) using synthetic genetic array technology and found chromatin remodellers and modifiers as an enriched category. In agreement with related studies, H2A.Z-encoding <i>HTZ1</i>, and the components of SWR1, INO80, and SAGA complexes represented prominent interactors, with <i>htz1</i> conferring the strongest growth defect. Because the truncation of Prp45 disproportionately affected low copy number transcripts of intron-containing genes, we prepared strains carrying intronless versions of <i>SRB2</i>, <i>VPS75</i>, or <i>HRB1</i>, the most affected cases with transcription-related function. Intron removal from <i>SRB2</i>, but not from the other genes, partly repaired some but not all the growth phenotypes identified in the genetic screen. The interaction of <i>prp45</i>(1-169) and <i>htz1</i>Δ was detectable even in cells with <i>SRB2</i> intron deleted (<i>srb2</i>Δi). The less truncated variant, <i>prp45</i>(1-330), had a synthetic growth defect with <i>htz1</i>Δ at 16°C, which also persisted in the <i>srb2</i>Δi background. Moreover, <i>htz1</i>Δ enhanced <i>prp45</i>(1-330) dependent pre-mRNA hyper-accumulation of both high and low efficiency splicers, genes <i>ECM33</i> and <i>COF1</i>, respectively. We conclude that while the expression defects of low expression intron-containing genes contribute to the genetic interactome of <i>prp45</i>(1-169), the genetic interactions between <i>prp45</i> and <i>htz1</i> alleles demonstrate the sensitivity of spliceosome assembly, delayed in <i>prp45</i>(1-169), to the chromatin environment.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868056","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}

{"title":"LncRNA USP2-AS1 facilitates the osteogenic differentiation of bone marrow mesenchymal stem cells by targeting KDM3A/ETS1/USP2 to activate the Wnt/β-catenin signaling pathway.","authors":"Wanxin Luo, Na Zhang, Ziping Wang, Hao Chen, Jie Sun, Chen Yao, Yafeng Zhang","doi":"10.1080/15476286.2023.2290771","DOIUrl":"10.1080/15476286.2023.2290771","url":null,"abstract":"<p><p>Human bone marrow mesenchymal stem cells (HBMSCs) can promote new bone formation. Previous studies have proven the ability of long non-coding RNAs (lncRNAs) to modulate the osteogenic differentiation of mesenchymal stem cells. However, the molecular mechanism modulated by lncRNAs in affecting the osteogenic differentiation of HBMSCs remains largely unknown. Thus, this study aims to reveal the role of lncRNA ubiquitin-specific peptidase 2 antisense RNA 1 (USP2-AS1) in regulating the osteogenic differentiation of HBMSCs and investigate its regulatory mechanism. Through bioinformatics analysis and RT-qPCR, we confirmed that USP2-AS1 expression was increased in HBMSCs after culturing in osteogenic differentiation medium (OM-HBMSCs). Moreover, we uncovered that knockdown of USP2-AS1 inhibited the osteogenic differentiation of HBMSCs. Further exploration indicated that USP2-AS1 positively regulated the expression of its nearby gene USP2. Mechanistically, USP2-AS1 recruited lysine demethylase 3A (KDM3A) to stabilize ETS proto-oncogene 1 (ETS1), transcription factor that transcriptionally activated USP2. Additionally, USP2-induced Wnt/β-catenin signalling pathway activation via deubiquitination of β-catenin protein. In summary, our study proved that lncRNA USP2-AS1 facilitates the osteogenic differentiation of HBMSCs by targeting KDM3A/ETS1/USP2 axis to activate the Wnt/β-catenin signalling pathway.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138831336","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}

{"title":"A comparative survey of the influence of small self-cleaving ribozymes on gene expression in human cell culture.","authors":"Dennis Kläge, Elisabeth Müller, Jörg S Hartig","doi":"10.1080/15476286.2023.2296203","DOIUrl":"10.1080/15476286.2023.2296203","url":null,"abstract":"<p><p>Self-cleaving ribozymes are versatile tools for synthetic biologists when it comes to controlling gene expression. Up to date, 12 different classes are known, and over the past decades more and more details about their structure, cleavage mechanisms and natural environments have been uncovered. However, when these motifs are applied to mammalian gene expression constructs, the outcome can often be unexpected. A variety of factors, such as surrounding sequences and positioning of the ribozyme influences the activity and hence performance of catalytic RNAs. While some information about the efficiency of individual ribozymes (each tested in specific contexts) is known, general trends obtained from standardized, comparable experiments are lacking, complicating decisions such as which ribozyme to choose and where to insert it into the target mRNA. In many cases, application-specific optimization is required, which can be very laborious. Here, we systematically compared different classes of ribozymes within the 3'-UTR of a given reporter gene. We then examined position-dependent effects of the best-performing ribozymes. Moreover, we tested additional variants of already widely used hammerhead ribozymes originating from various organisms. We were able to identify functional structures suited for aptazyme design and generated highly efficient hammerhead ribozyme variants originating from the human genome. The present dataset will aide decisions about how to apply ribozymes for affecting gene expression as well as for developing ribozyme-based switches for controlling gene expression in human cells.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037971","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}

{"title":"Multiple roles for AU-rich RNA binding proteins in the development of haematologic malignancies and their resistance to chemotherapy.","authors":"Paulina Podszywalow-Bartnicka, Karla M Neugebauer","doi":"10.1080/15476286.2024.2346688","DOIUrl":"10.1080/15476286.2024.2346688","url":null,"abstract":"<p><p>Post-transcriptional regulation by RNA binding proteins can determine gene expression levels and drive changes in cancer cell proteomes. Identifying mechanisms of protein-RNA binding, including preferred sequence motifs bound <i>in vivo</i>, provides insights into protein-RNA networks and how they impact mRNA structure, function, and stability. In this review, we will focus on proteins that bind to AU-rich elements (AREs) in nascent or mature mRNA where they play roles in response to stresses encountered by cancer cells. ARE-binding proteins (ARE-BPs) specifically impact alternative splicing, stability, decay and translation, and formation of RNA-rich biomolecular condensates like cytoplasmic stress granules (SGs). For example, recent findings highlight the role of ARE-BPs - like TIAR and HUR - in chemotherapy resistance and in translational regulation of mRNAs encoding pro-inflammatory cytokines. We will discuss emerging evidence that different modes of ARE-BP activity impact leukaemia and lymphoma development, progression, adaptation to microenvironment and chemotherapy resistance.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11135835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155412","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}

{"title":"MRM-BERT: a novel deep neural network predictor of multiple RNA modifications by fusing BERT representation and sequence features.","authors":"Linshu Wang, Yuan Zhou","doi":"10.1080/15476286.2024.2315384","DOIUrl":"10.1080/15476286.2024.2315384","url":null,"abstract":"<p><p>RNA modifications play crucial roles in various biological processes and diseases. Accurate prediction of RNA modification sites is essential for understanding their functions. In this study, we propose a hybrid approach that fuses a pre-trained sequence representation with various sequence features to predict multiple types of RNA modifications in one combined prediction framework. We developed MRM-BERT, a deep learning method that combined the pre-trained DNABERT deep sequence representation module and the convolutional neural network (CNN) exploiting four traditional sequence feature encodings to improve the prediction performance. MRM-BERT was evaluated on multiple datasets of 12 commonly occurring RNA modifications, including m⁶A, m⁵C, m¹A and so on. The results demonstrate that our hybrid model outperforms other models in terms of area under receiver operating characteristic curve (AUC) for all 12 types of RNA modifications. MRM-BERT is available as an online tool (http://117.122.208.21:8501) or source code (https://github.com/abhhba999/MRM-BERT), which allows users to predict RNA modification sites and visualize the results. Overall, our study provides an effective and efficient approach to predict multiple RNA modifications, contributing to the understanding of RNA biology and the development of therapeutic strategies.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10877979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736036","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}

{"title":"Alternative splicing events driven by altered levels of GEMIN5 undergo translation.","authors":"Rosario Francisco-Velilla, Salvador Abellan, Juan Antonio Garcia-Martin, Juan Carlos Oliveros, Encarnacion Martinez-Salas","doi":"10.1080/15476286.2024.2394755","DOIUrl":"10.1080/15476286.2024.2394755","url":null,"abstract":"<p><p>GEMIN5 is a multifunctional protein involved in various aspects of RNA biology, including biogenesis of snRNPs and translation control. Reduced levels of GEMIN5 confer a differential translation to selective groups of mRNAs, and biallelic variants reducing protein stability or inducing structural conformational changes are associated with neurological disorders. Here, we show that upregulation of GEMIN5 can be detrimental as it modifies the steady state of mRNAs and enhances alternative splicing (AS) events of genes involved in a broad range of cellular processes. RNA-Seq identification of the mRNAs associated with polysomes in cells with high levels of GEMIN5 revealed that a significant fraction of the differential AS events undergo translation. The association of mRNAs with polysomes was dependent on the type of AS event, being more frequent in the case of exon skipping. However, there were no major differences in the percentage of genes showing open-reading frame disruption. Importantly, differential AS events in mRNAs engaged in polysomes, eventually rendering non-functional proteins, encode factors controlling cell growth. The broad range of mRNAs comprising AS events engaged in polysomes upon GEMIN5 upregulation supports the notion that this multifunctional protein has evolved as a gene expression balancer, consistent with its dual role as a member of the SMN complex and as a modulator of protein synthesis, ultimately impinging on cell homoeostasis.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11364065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081387","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}

{"title":"Retrotransposon life cycle and its impacts on cellular responses.","authors":"Ahmad Luqman-Fatah, Kei Nishimori, Shota Amano, Yukiko Fumoto, Tomoichiro Miyoshi","doi":"10.1080/15476286.2024.2409607","DOIUrl":"https://doi.org/10.1080/15476286.2024.2409607","url":null,"abstract":"<p><p>Approximately 45% of the human genome is comprised of transposable elements (TEs), also known as mobile genetic elements. However, their biological function remains largely unknown. Among them, retrotransposons are particularly abundant, and some of the copies are still capable of mobilization within the genome through RNA intermediates. This review focuses on the life cycle of human retrotransposons and summarizes their regulatory mechanisms and impacts on cellular processes. Retrotransposons are generally epigenetically silenced in somatic cells, but are transcriptionally reactivated under certain conditions, such as tumorigenesis, development, stress, and ageing, potentially leading to genetic instability. We explored the dual nature of retrotransposons as genomic parasites and regulatory elements, focusing on their roles in genetic diversity and innate immunity. Furthermore, we discuss how host factors regulate retrotransposon RNA and cDNA intermediates through their binding, modification, and degradation. The interplay between retrotransposons and the host machinery provides insight into the complex regulation of retrotransposons and the potential for retrotransposon dysregulation to cause aberrant responses leading to inflammation and autoimmune diseases.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473696","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}

{"title":"Correction.","authors":"","doi":"10.1080/15476286.2024.2413227","DOIUrl":"10.1080/15476286.2024.2413227","url":null,"abstract":"","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392931","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}