{"title":"The regulatory roles of RNA-binding proteins in the tumour immune microenvironment of gastrointestinal malignancies.","authors":"Dongqi Li, Xiangyu Chu, Weikang Liu, Yongsu Ma, Xiaodong Tian, Yinmo Yang","doi":"10.1080/15476286.2024.2440683","DOIUrl":"10.1080/15476286.2024.2440683","url":null,"abstract":"<p><p>The crosstalk between the tumour immune microenvironment (TIME) and tumour cells promote immune evasion and resistance to immunotherapy in gastrointestinal (GI) tumours. Post-transcriptional regulation of genes is pivotal to GI tumours progression, and RNA-binding proteins (RBPs) serve as key regulators via their RNA-binding domains. RBPs may exhibit either anti-tumour or pro-tumour functions by influencing the TIME through the modulation of mRNAs and non-coding RNAs expression, as well as post-transcriptional modifications, primarily N6-methyladenosine (m<sup>6</sup>A). Aberrant regulation of RBPs, such as HuR and YBX1, typically enhances tumour immune escape and impacts prognosis of GI tumour patients. Further, while targeting RBPs offers a promising strategy for improving immunotherapy in GI cancers, the mechanisms by which RBPs regulate the TIME in these tumours remain poorly understood, and the therapeutic application is still in its early stages. This review summarizes current advances in exploring the roles of RBPs in regulating genes expression and their effect on the TIME of GI tumours, then providing theoretical insights for RBP-targeted cancer therapies.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882916","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: 2024-12-26DOI: 10.1080/15476286.2024.2442856
Minjie Zhang, Zhipeng Lu
{"title":"tRNA modifications: greasing the wheels of translation and beyond.","authors":"Minjie Zhang, Zhipeng Lu","doi":"10.1080/15476286.2024.2442856","DOIUrl":"https://doi.org/10.1080/15476286.2024.2442856","url":null,"abstract":"<p><p>Transfer RNA (tRNA) is one of the most abundant RNA types in cells, acting as an adaptor to bridge the genetic information in mRNAs with the amino acid sequence in proteins. Both tRNAs and small fragments processed from them play many nonconventional roles in addition to translation. tRNA molecules undergo various types of chemical modifications to ensure the accuracy and efficiency of translation and regulate their diverse functions beyond translation. In this review, we discuss the biogenesis and molecular mechanisms of tRNA modifications, including major tRNA modifications, writer enzymes, and their dynamic regulation. We also summarize the state-of-the-art technologies for measuring tRNA modification, with a particular focus on 2'-O-methylation (Nm), and discuss their limitations and remaining challenges. Finally, we highlight recent discoveries linking dysregulation of tRNA modifications with genetic diseases.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-25"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897124","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":"Prp16 enables efficient splicing of introns with diverse exonic consensus elements in the short-intron rich <i>Cryptococcus neoformans</i> transcriptome.","authors":"Manendra Singh Negi, Vishnu Priya Krishnan, Niharika Saraf, Usha Vijayraghavan","doi":"10.1080/15476286.2025.2477844","DOIUrl":"10.1080/15476286.2025.2477844","url":null,"abstract":"<p><p>DEAH box splicing helicase Prp16 in budding yeast governs spliceosomal remodelling from the branching conformation (C complex) to the exon ligation conformation (C* complex). In this study, we examined the genome-wide functions of Prp16 in the short intron-rich genome of the basidiomycete yeast <i>Cryptococcus neoformans</i>. The presence of multiple introns per transcript with intronic features that are more similar to those of higher eukaryotes makes it a promising model for studying spliceosomal splicing. Using a promoter-shutdown conditional Prp16 knockdown strain, we uncovered genome-wide but substrate-specific roles in <i>C. neoformans</i> splicing. The splicing functions of Prp16 are dependent on helicase motifs I and II, which are conserved motifs for helicase activity. A small subset of introns spliced independent of Prp16 activity was investigated to discover that exonic sequences at the 5' splice site (5'SS) and 3' splice site (3'SS) with stronger affinity for U5 loop 1 are a common feature in these introns. Furthermore, short (60-100nts) and ultrashort introns (<60nts) prevalent in the <i>C. neoformans</i> transcriptome were more sensitive to Prp16 knockdown than longer introns, indicating that Prp16 is required for the efficient splicing of short and ultrashort introns. We propose that stronger U5 snRNA-pre-mRNA interactions enable efficient transition of the spliceosome from the first to the second catalytic confirmation in Prp16 knockdown, particularly for short introns and introns with suboptimal features. This study provides insights into fine-tuning spliceosomal helicase function with variations in <i>cis-</i>element features.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597670","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: 2025-03-02DOI: 10.1080/15476286.2025.2472448
Nils Peiter, Anna Einert, Pauline Just, Frida Jannasch, Marija Najdovska, Michael Rother
{"title":"Defining the methanogenic SECIS element <i>in vivo</i> by targeted mutagenesis.","authors":"Nils Peiter, Anna Einert, Pauline Just, Frida Jannasch, Marija Najdovska, Michael Rother","doi":"10.1080/15476286.2025.2472448","DOIUrl":"10.1080/15476286.2025.2472448","url":null,"abstract":"<p><p>In all domains of life, Archaea, Eukarya and Bacteria, the unusual amino acid selenocysteine (Sec) is co-translationally incorporated into proteins by recoding a UGA stop codon to a sense codon. A secondary structure on the mRNA, the selenocysteine insertion sequence (SECIS), is required, but its position, secondary structure and binding partner(s) are not conserved across the tree of life. Thus far, the nature of archaeal SECIS elements has been derived mainly from sequence analyses. A recently developed <i>in vivo</i> reporter system was used to study the structure-function relationships of SECIS elements in <i>Methanococcus maripaludis</i>. Through targeted mutagenesis, we defined the minimal functional SECIS element, the parts of the SECIS where structure and not the identity of the bases are relevant for function, and identified two conserved -and invariant- adenines that are most likely to interact with the other factor(s) of the Sec recoding machinery. Finally, we demonstrated the functionality of SECIS elements in the 5`-untranslated region of the mRNA and identified a potential mechanism of SECIS repositioning in the vicinity of the UGA for efficient selenocysteine insertion.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-13"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503658","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: 2025-01-11DOI: 10.1080/15476286.2025.2449775
Martin Hart, Caroline Diener, Stefanie Rheinheimer, Tim Kehl, Andreas Keller, Hans-Peter Lenhof, Eckart Meese
{"title":"Expanding the immune-related targetome of miR-155-5p by integrating time-resolved RNA patterns into miRNA target prediction.","authors":"Martin Hart, Caroline Diener, Stefanie Rheinheimer, Tim Kehl, Andreas Keller, Hans-Peter Lenhof, Eckart Meese","doi":"10.1080/15476286.2025.2449775","DOIUrl":"10.1080/15476286.2025.2449775","url":null,"abstract":"<p><p>The lack of a sufficient number of validated miRNA targets severely hampers the understanding of their biological function. Even for the well-studied miR-155-5p, there are only 239 experimentally validated targets out of 42,554 predicted targets. For a more complete assessment of the immune-related miR-155 targetome, we used an inverse correlation of time-resolved mRNA profiles and miR-155-5p expression of early CD4+ T cell activation to predict immune-related target genes. Using a high-throughput miRNA interaction reporter (HiTmIR) assay we examined 90 target genes and confirmed 80 genes as direct targets of miR-155-5p. Our study increases the current number of verified miR-155-5p targets approximately threefold and exemplifies a method for verifying miRNA targetomes as a prerequisite for the analysis of miRNA-regulated cellular networks.</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/PMC11730359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932646","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: 10.1080/15476286.2024.2449278
Waqasuddin Khan, Samiah Kanwar, Mohammad Mohsin Mannan, Furqan Kabir, Naveed Iqbal, Mehdia Nadeem Rajab Ali, Syeda Rehana Zia, Sharmeen Mian, Fatima Aziz, Sahrish Muneer, Adil Kalam, Akram Hussain, Iqra Javed, Muhammad Farrukh Qazi, Javairia Khalid, Muhammad Imran Nisar, Fyezah Jehan
{"title":"Identification of differentially expressed non-coding RNAs in the plasma of women with preterm birth.","authors":"Waqasuddin Khan, Samiah Kanwar, Mohammad Mohsin Mannan, Furqan Kabir, Naveed Iqbal, Mehdia Nadeem Rajab Ali, Syeda Rehana Zia, Sharmeen Mian, Fatima Aziz, Sahrish Muneer, Adil Kalam, Akram Hussain, Iqra Javed, Muhammad Farrukh Qazi, Javairia Khalid, Muhammad Imran Nisar, Fyezah Jehan","doi":"10.1080/15476286.2024.2449278","DOIUrl":"10.1080/15476286.2024.2449278","url":null,"abstract":"<p><p>This study aimed to identify differentially expressed non-coding RNAs (ncRNAs) associated with preterm birth (PTB) and determine biological pathways being influenced in the context of PTB. We processed cell-free RNA sequencing data and identified seventeen differentially expressed (DE) ncRNAs that could be involved in the onset of PTB. Per the validation via customized RT-qPCR, the recorded variations in expressions of eleven ncRNAs were concordant with the <i>in-silico</i> analyses. The results of this study provide insights into the role of DE ncRNAs and their impact on pregnancy-related biological pathways that could lead to PTB. Further studies are required to elucidate the precise mechanisms by which these DE ncRNAs contribute to adverse pregnancy outcomes (APOs) and their potential as diagnostic biomarkers.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-8"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971981","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: 2024-12-23DOI: 10.1080/15476286.2024.2443876
Yan Yang, Yinchun Zhong, Liang Chen
{"title":"EIciRNAs in focus: current understanding and future perspectives.","authors":"Yan Yang, Yinchun Zhong, Liang Chen","doi":"10.1080/15476286.2024.2443876","DOIUrl":"10.1080/15476286.2024.2443876","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are a unique class of covalently closed single-stranded RNA molecules that play diverse roles in normal physiology and pathology. Among the major types of circRNA, exon-intron circRNA (EIciRNA) distinguishes itself by its sequence composition and nuclear localization. Recent RNA-seq technologies and computational methods have facilitated the detection and characterization of EIciRNAs, with features like circRNA intron retention (CIR) and tissue-specificity being characterized. EIciRNAs have been identified to exert their functions via mechanisms such as regulating gene transcription, and the physiological relevance of EIciRNAs has been reported. Within this review, we present a summary of the current understanding of EIciRNAs, delving into their identification and molecular functions. Additionally, we emphasize factors regulating EIciRNA biogenesis and the physiological roles of EIciRNAs based on recent research. We also discuss the future challenges in EIciRNA exploration, underscoring the potential for novel functions and functional mechanisms of EIciRNAs for further investigation.</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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877855","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: 2025-02-13DOI: 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":"","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":"","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}