RNA BiologyPub Date : 2025-12-01Epub Date: 2025-02-13DOI: 10.1080/15476286.2025.2465196
Vincent G Osnaya, Laura Gómez-Romero, Gabriel Moreno-Hagelsieb, Greco Hernández
{"title":"AUGcontext DB: a comprehensive catalog of the mRNA AUG initiator codon context across eukaryotes.","authors":"Vincent G Osnaya, Laura Gómez-Romero, Gabriel Moreno-Hagelsieb, Greco Hernández","doi":"10.1080/15476286.2025.2465196","DOIUrl":"10.1080/15476286.2025.2465196","url":null,"abstract":"<p><p>The mRNA translation defines the composition of the cell proteome in all forms of life and diseases. In this process, precise selection of the mRNA translation initiation site (TIS) is crucial, as it establishes the correct open reading frame for triplet decoding. We have gathered and curated all published TIS consensus context sequences. We also included the TIS consensus context from novel 538 fungal genomes available from NCBI's RefSeq database. To do so, we wrote ad hoc programs in PERL to find and extract the TIS for each annotated gene, plus ten bases upstream and three downstream. For each genome, the sequences around the TIS of each gene were obtained, and the consensus was further calculated according to the Cavener rules and by the LOGOS algorithm. We created AUGcontext DB, a portal with a comprehensive collection of TIS context sequences across eukaryotes in a range from -10 to + 6. The compilation covers species of 30 vertebrates, 17 invertebrates, 25 plants, 14 fungi, and 11 protists studied in silico; 23 experimental studies; data on biotechnology; and the discovery of 8 diseases associated with specific mutations. Additionally, TIS context sequences of cellular IRESs were included. AUGcontext DB belongs to the National Institute of Cancer (Instituto Nacional de Cancerología, INCan), Mexico, and is freely available at http://108.161.138.77:8096/. Our catalogue allows us to do comparative studies between species, may help improve the diagnosis of certain diseases, and will be key to maximize the production of recombinant proteins.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-5"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399899","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 HOTAIR promotes aerobic glycolysis by recruiting Lin28 to induce inflammation and apoptosis in acute lung injury.","authors":"Junjie Xie, Zhicong Zheng, Bin Wang, Jianfang Zhang, Junqi Jiang, Fengde Wu, Xiangming Zhong, Jianfeng Chen","doi":"10.1080/15476286.2025.2475255","DOIUrl":"10.1080/15476286.2025.2475255","url":null,"abstract":"<p><p>Acute lung injury (ALI) is a life-threatening condition with high rates of morbidity and mortality. Recently, there has been growing evidence suggesting a link between lncRNA HOTAIR and ALI. Nonetheless, the precise role and mechanism of lncRNA HOTAIR in ALI remain to be fully elucidated. siHOTAIR transfection, qPCR detection (HOTAIR), ELISA (TNF-α, IL-6, and IL-1β), Lactate detection, Glucose uptake experiment, Cell Apoptosis Analysis, Fluorescence in situ hybridization (FISH) assay. Through siHOTAIR transfection, we discovered that HOTAIR plays a role in the secretion of inflammatory factors in ALI and further regulates glucose uptake and metabolism in lung epithelial cells. Moreover, a comparison between HOTAIR knockdown cells and HOTAIR overexpression cells revealed that HOTAIR promotes cellular aerobic sugar metabolism, leading to increased secretion of inflammatory factors and cell apoptosis. Our in-depth research also identified an interaction between HOTAIR and the LIN28 protein. Knocking down HOTAIR resulted in the downregulation of LIN28 protein expression, which subsequently inhibited the expression of the glucose transporter GLUT1. This indicates that HOTAIR facilitates glucose uptake and boosts cellular aerobic glycolysis by modulating the LIN28 protein, thereby promoting inflammation and apoptosis in acute lung injury. The research findings presented in this article offer significant insights into the function of HOTAIR in ALI and suggest a potential therapeutic target for the treatment of this condition.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-12"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573924","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}
RNA BiologyPub Date : 2025-12-01Epub Date: 2025-01-13DOI: 10.1080/15476286.2024.2448391
Jan-Niklas Tants, Katharina Friedrich, Jasmina Neumann, Andreas Schlundt
{"title":"Evolution of the RNA alternative decay <i>cis</i> element into a high-affinity target for the immunomodulatory protein Roquin.","authors":"Jan-Niklas Tants, Katharina Friedrich, Jasmina Neumann, Andreas Schlundt","doi":"10.1080/15476286.2024.2448391","DOIUrl":"https://doi.org/10.1080/15476286.2024.2448391","url":null,"abstract":"<p><p>RNA <i>cis</i> elements play pivotal roles in regulatory processes, e.g. in transcriptional and translational regulation. Two stem-looped <i>cis</i> elements, the constitutive and alternative decay elements (CDE and ADE, respectively) are shape-specifically recognized in mRNA 3' untranslated regions (UTRs) by the immune-regulatory protein Roquin. Roquin initiates mRNA decay and contributes to balanced transcript levels required for immune homoeostasis. While the interaction of Roquin with several CDEs is described, our knowledge about ADE complex formation is limited to the mRNA of <i>Ox40</i>, a gene encoding a T-cell costimulatory receptor. The <i>Ox40</i> 3'UTR comprises both a CDE and ADE, each sufficient for Roquin-mediated control. Opposed to highly conserved and abundant CDE structures, ADEs are rarer, but predicted to exhibit a greater structural heterogeneity. This raises the question of how and when two structurally distinct <i>cis</i> elements evolved as equal target motifs for Roquin. Using an interdisciplinary approach, we here monitor the evolution of sequence and structure features of the <i>Ox40</i> ADE across species. We designed RNA variants to probe en-detail determinants steering Roquin-RNA complex formation. Specifically, those reveal the contribution of a second RNA-binding interface of Roquin for recognition of the ADE basal stem region. In sum, our study sheds light on how the conserved Roquin protein selected ADE-specific structural features to evolve a second high-affinity mRNA target <i>cis</i> element relevant for adaptive immune regulation. As our findings also allow expanding the RNA target spectrum of Roquin, the approach can serve a paradigm for understanding RNA-protein specificity through back-tracing the evolution of the RNA element.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-12"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056062","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}
RNA BiologyPub Date : 2025-12-01Epub Date: 2024-12-13DOI: 10.1080/15476286.2024.2437590
Betül Akçeşme, Hilal Hekimoğlu, Venkat R Chirasani, Şeyma İş, Habibe Nur Atmaca, Justin M Waldern, Silvia B V Ramos
{"title":"Identification of deleterious non-synonymous single nucleotide polymorphisms in the mRNA decay activator ZFP36L2.","authors":"Betül Akçeşme, Hilal Hekimoğlu, Venkat R Chirasani, Şeyma İş, Habibe Nur Atmaca, Justin M Waldern, Silvia B V Ramos","doi":"10.1080/15476286.2024.2437590","DOIUrl":"10.1080/15476286.2024.2437590","url":null,"abstract":"<p><p>More than 4,000 single nucleotide polymorphisms (SNP) variants have been identified in the human <i>ZFP36L2</i> gene, however only a few have been studied in the context of protein function. The tandem zinc finger domain of ZFP36L2, an RNA binding protein, is the functional domain that binds to its target mRNAs. This protein/RNA interaction triggers mRNA degradation, controlling gene expression. We identified 32 non-synonymous SNPs (nsSNPs) in the tandem zinc finger domain of ZFP36L2 that could have possible deleterious impacts in humans. Using different bioinformatic strategies, we prioritized five among these 32 nsSNPs, namely rs375096815, rs1183688047, rs1214015428, rs1215671792 and rs920398592 to be validated. When we experimentally tested the functionality of these protein variants using gel shift assays, all five (Y154H, R160W, R184C, G204D, and C206F) resulted in a dramatic reduction in RNA binding compared to the WT protein. To understand the mechanistic effect of these variants on the protein/RNA interaction, we employed DUET, DynaMut and PyMOL to investigate structural changes in the protein. Additionally, we conducted Molecular Docking and Molecular Dynamics Simulations to fine tune the active behaviour of this biomolecular system at an atomic level. Our results propose atomic explanations for the impact of each of these five genetic variants identified.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-15"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819035","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}
RNA BiologyPub Date : 2025-12-01Epub Date: 2025-02-06DOI: 10.1080/15476286.2025.2462276
Hoang-Anh Pham-Bui, Mihye Lee
{"title":"Germ granule-mediated mRNA storage and translational control.","authors":"Hoang-Anh Pham-Bui, Mihye Lee","doi":"10.1080/15476286.2025.2462276","DOIUrl":"10.1080/15476286.2025.2462276","url":null,"abstract":"<p><p>Germ cells depend on specialized post-transcriptional regulation for proper development and function, much of which is mediated by dynamic RNA granules. These membrane-less organelles form through the condensation of RNA and proteins, governed by multivalent biomolecular interactions. RNA granules compartmentalize cellular components, selectively enriching specific factors and modulating biochemical reactions. Over recent decades, various types of RNA granules have been identified in germ cells across species, with extensive studies uncovering their molecular roles and developmental significance. This review explores the mRNA regulatory mechanisms mediated by RNA granules in germ cells. We discuss the distinct spatial organization of specific granule components and the variations in material states of germ granules, which contribute to the regulation of mRNA storage and translation. Additionally, we highlight emerging research on how changes in these material states, during developmental stages, reflect the dynamic nature of germ granules and their critical role in development.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-11"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080907","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}
RNA BiologyPub Date : 2025-12-01Epub Date: 2025-02-11DOI: 10.1080/15476286.2025.2459039
Pavel Vopalensky, Anton Škríba, Michela Chiumenti, Lucia Ďuričeková, Anna Šimonová, Ondřej Lukšan, Francesco Di Serio, Beatriz Navarro, Hana Cahova
{"title":"Exploring RNA modifications in infectious non-coding circular RNAs.","authors":"Pavel Vopalensky, Anton Škríba, Michela Chiumenti, Lucia Ďuričeková, Anna Šimonová, Ondřej Lukšan, Francesco Di Serio, Beatriz Navarro, Hana Cahova","doi":"10.1080/15476286.2025.2459039","DOIUrl":"10.1080/15476286.2025.2459039","url":null,"abstract":"<p><p>Viroids, small circular non-coding RNAs, act as infectious pathogens in higher plants, demonstrating high stability despite consisting solely of naked RNA. Their dependence of replication on host machinery poses the question of whether RNA modifications play a role in viroid biology. Here, we explore RNA modifications in the avocado sunblotch viroid (ASBVd) and the citrus exocortis viroid (CEVd), representative members of viroids replicating in chloroplasts and the nucleus, respectively, using LC - MS and Oxford Nanopore Technology (ONT) direct RNA sequencing. Although no modification was detected in ASBVd, CEVd contained approximately one m<sup>6</sup>A per RNA molecule. ONT sequencing predicted three m<sup>6</sup>A positions. Employing orthogonal SELECT method, we confirmed m<sup>6</sup>A in two positions A353 and A360, which are highly conserved among CEVd variants. These positions are located in the left terminal region of the CEVd rod-like structure where likely RNA Pol II and and TFIIIA-7ZF bind, thus suggesting potential biological role of methylation in viroid replication.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-9"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067876","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}
RNA BiologyPub Date : 2025-12-01Epub Date: 2025-03-31DOI: 10.1080/15476286.2025.2483118
Danielle Rayêe, U Thomas Meier, Carolina Eliscovich, Aleš Cvekl
{"title":"Nucleolar ribosomal RNA synthesis continues in differentiating lens fiber cells until abrupt nuclear degradation required for ocular lens transparency.","authors":"Danielle Rayêe, U Thomas Meier, Carolina Eliscovich, Aleš Cvekl","doi":"10.1080/15476286.2025.2483118","DOIUrl":"10.1080/15476286.2025.2483118","url":null,"abstract":"<p><p>Cellular differentiation requires highly coordinated action of all three transcriptional systems to produce rRNAs, mRNAs and various 'short' and 'long' non-coding RNAs by RNA Polymerase I, II and III systems, respectively. RNA Polymerase I catalyzes transcription of about 400 copies of mammalian rDNA genes, generating 18S, 5.8S and 28S rRNA molecules. Lens fiber cell differentiation is a unique process to study transcriptional mechanisms of individual crystallin genes as their very high transcriptional outputs are directly comparable only to globin genes in erythrocytes. Importantly, both terminally differentiated lens fiber cells and mammalian erythrocytes degrade their nuclei through different mechanisms. In lens, the generation of the organelle-free zone (OFZ) includes the degradation of mitochondria, endoplasmic reticulum, Golgi apparatus and nuclei. Here, using RNA fluorescence <i>in situ</i> hybridization (FISH), we evaluated nascent rRNA transcription, located in the nucleoli, during the process of mouse lens fiber cell differentiation. Lens fiber cell nuclei undergo morphological changes including chromatin condensation prior to their denucleation. Remarkably, nascent rRNA transcription persists in all nuclei that are in direct proximity of the OFZ. Additionally, changes in both nuclei and nucleoli shape were evaluated via immunofluorescence detection of fibrillarin, nucleolin, UBF and other proteins. These studies demonstrate for the first time that highly condensed lens fiber cell nuclei have the capacity to support nascent rRNA transcription. Thus, we propose that 'late' production of rRNA molecules and consequently of ribosomes increases crystallin protein synthesis machinery within the mature lens fibers.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-16"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691809","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}
{"title":"RNA diagnostics and therapeutics: a comprehensive review.","authors":"Adeela Fathima Saju, Aditi Mukundan, Divyashree Ms, Raghu Chandrashekhar, Archana Mahadev Rao","doi":"10.1080/15476286.2024.2449277","DOIUrl":"10.1080/15476286.2024.2449277","url":null,"abstract":"<p><p>RNA-focused therapy and diagnostics have been making waves in molecular biology due to the advantages RNA has over DNA; for instance, the ability of RNA to target nearly any genetic component in the cell is a big step in treating disorders. Moreover, RNA-based diagnosis of diseases is only becoming increasingly popular, especially after the COVID-19 pandemic, which brought up the need for cost-effective and efficient diagnosing kits for the vast majority. RNA-based techniques also have close to no risk of genotoxicity and can efficiently target undruggable regions of the cell. RNA treatments have effectively shown the future of the medical industry in the past couple of decades, and they will only be seen to improve. This review paper provides an overview on the different techniques that use RNA-based approaches in the field of diagnostics and therapeutics.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-11"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915525","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}
RNA BiologyPub Date : 2025-12-01Epub Date: 2024-12-24DOI: 10.1080/15476286.2024.2446868
Thong Teck Tan, Sai Kiang Lim
{"title":"Relevance of RNA to the therapeutic efficacy of mesenchymal stromal/stem cells extracellular vesicles.","authors":"Thong Teck Tan, Sai Kiang Lim","doi":"10.1080/15476286.2024.2446868","DOIUrl":"10.1080/15476286.2024.2446868","url":null,"abstract":"<p><p>Mesenchymal Stromal/Stem Cells (MSCs) are among the most frequently studied cell types in clinical trials, and their small extracellular vesicles (sEVs) are now being extensively investigated for therapeutic applications. The RNA cargo of MSC-sEVs, particularly miRNAs and mRNAs, is widely believed to be a key therapeutic component of these vesicles. In this review, we critically examine using first principles and peer-reviewed literature, whether MSC- extracellular vesicles (MSC-EVs) can deliver sufficient quantity of functional miRNA or mRNA to target compartments within recipient cells to elicit a pharmacological response. Several RNA sequencing studies reveal that miRNAs are underrepresented in the small RNA population of MSC-sEVs compared to the parent MSCs. Additionally, the majority of miRNAs are mature forms that are not associated with Argonaute (AGO) proteins, essential for their function in RNA-induced silencing complexes (RISCs). Compounding this, cellular uptake of EVs is generally inefficient, with less than 1% being internalized, and only a fraction of these reaching the cytosol. This suggests that EVs may not deliver miRNAs in sufficient quantities to meaningfully interact with AGO proteins, either through canonical or non-canonical pathways, or with other proteins like Toll-like receptors (TLRs). Further, MSC-sEV RNAs are generally small, with sizes less than 500 nucleotides indicating that any mRNA present is likely fragmented as the average mammalian mRNA is approximately 2000 nucleotides, a fact confirmed by RNA sequencing data. Together, these findings challenge the notion that RNA, particularly miRNAs and mRNAs, are primary therapeutic attributes of MSC-sEVs.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-7"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885343","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}