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":"21 1","pages":"11-22"},"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":"21 1","pages":"1-10"},"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":"Post-transcriptional regulation of BIRC5/survivin expression and induction of apoptosis in breast cancer cells by tristetraprolin.","authors":"Suhad Al-Yahya, Maher Al-Saif, Maha Al-Ghamdi, Walid Moghrabi, Khalid S A Khabar, Norah Al-Souhibani","doi":"10.1080/15476286.2023.2286101","DOIUrl":"10.1080/15476286.2023.2286101","url":null,"abstract":"<p><p>Inhibition of apoptosis is one of the hallmarks of cancer and is a target of various therapeutic interventions. BIRC5 is an inhibitor of apoptosis that is aberrantly expressed in cancer leading to sustained growth of tumours. Post-transcriptional control mechanisms involving RNA-binding proteins and AU-rich elements (AREs) are fundamental to many cellular processes and changes in the expression or function of these proteins can promote an aberrant and pathological phenotype. BIRC5 mRNA has an ARE in its 3' UTR making it a candidate for regulation by the RNA binding proteins tristetraprolin (TTP) and HuR (ELAVL1). In this study, we investigated the binding of TTP and HuR by RNA-immunoprecipitation assays and found that these proteins were associated with BIRC5 mRNA to varying extents. Consequently, BIRC5 expression decreased when TTP was overexpressed and apoptosis was induced. In the absence of TTP, BIRC5 mRNA was stabilized, protein expression increased and the number of apoptotic cells declined. As an ARE-mRNA stabilizing protein, recombinant HuR led to upregulation of BIRC5 expression, whereas HuR silencing was concomitant with downregulation of BIRC5 mRNA and protein and increased cell death. Survival analyses demonstrated that increased TTP and low BIRC5 expression predicted an overall better prognosis compared to dysregulated TTP and high BIRC5. Thus, the results present a novel target of ARE-mediated post-transcriptional regulation.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"21 1","pages":"1-15"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138809127","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":"Programmable RNA targeting with CRISPR-Cas13.","authors":"Peiguo Shi, Xuebing Wu","doi":"10.1080/15476286.2024.2351657","DOIUrl":"10.1080/15476286.2024.2351657","url":null,"abstract":"<p><p>The RNA-targeting CRISPR-Cas13 system has enabled precise engineering of endogenous RNAs, significantly advancing our understanding of RNA regulation and the development of RNA-based diagnostic and therapeutic applications. This review aims to provide a summary of Cas13-based RNA targeting tools and applications, discuss limitations and challenges of existing tools and suggest potential directions for further development of the RNA targeting system.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"21 1","pages":"1-9"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065794","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":"Decoding the genome of SARS-CoV-2: a pathway to drug development through translation inhibition.","authors":"Shan-Na Wu, Ting Xiao, Hui Chen, Xiao-Hong Li","doi":"10.1080/15476286.2024.2433830","DOIUrl":"10.1080/15476286.2024.2433830","url":null,"abstract":"<p><p>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19) pandemic and is continuously spreading globally. The continuous emergence of new SARS-CoV-2 variants keeps posing threats, highlighting the need for fast-acting, mutation-resistant broad-spectrum therapeutics. Protein translation is vital for SARS-CoV-2 replication, producing early non-structural proteins for RNA replication and transcription, and late structural proteins for virion assembly. Targeted blocking of viral protein translation is thus a potential approach to developing effective anti-SARS-CoV-2 drugs. SARS-CoV-2, as an obligate parasite, utilizes the host's translation machinery. Translation-blocking strategies that target the SARS-CoV-2 mRNA, especially those that target its conserved elements are generally preferred. In this review, we discuss the current understanding of SARS-CoV-2 translation, highlighting the important conserved motifs and structures involved in its regulation. We also discuss the current strategies for blocking SARS-CoV-2 translation through viral RNA degradation or RNA element dysfunction.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"21 1","pages":"1-18"},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772090","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":"21 1","pages":"1-13"},"PeriodicalIF":3.6,"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":"21 1","pages":"1-11"},"PeriodicalIF":3.6,"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":"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":"21 1","pages":"1-10"},"PeriodicalIF":3.6,"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":"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":"21 1","pages":"1-17"},"PeriodicalIF":3.6,"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":"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":"21 1","pages":"1-17"},"PeriodicalIF":3.6,"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}