RNA BiologyPub Date : 2025-12-01Epub Date: 2025-02-16DOI: 10.1080/15476286.2025.2463812
Sergei Funikov, Alexander Rezvykh, Natalia Akulenko, Jiangtao Liang, Igor V Sharakhov, Alla Kalmykova
{"title":"Analysis of somatic piRNAs in the malaria mosquito <i>Anopheles coluzzii</i> reveals atypical classes of genic small RNAs.","authors":"Sergei Funikov, Alexander Rezvykh, Natalia Akulenko, Jiangtao Liang, Igor V Sharakhov, Alla Kalmykova","doi":"10.1080/15476286.2025.2463812","DOIUrl":"10.1080/15476286.2025.2463812","url":null,"abstract":"<p><p>Piwi-interacting small RNAs (piRNA) play a key role in controlling the activity of transposable elements (TEs) in the animal germline. In diverse arthropod species, including the pathogen vectors mosquitoes, the piRNA pathway is also active in nongonadal somatic tissues, where its targets and functions are less clear. Here, we studied the features of small RNA production in head and thorax tissues of an uninfected laboratory strain of <i>Anopheles coluzzii</i> focusing on the 24-32-nt-long RNAs. Small RNAs derived from repetitive elements constitute a minor fraction while most small RNAs process from long noncoding RNAs (lncRNAs) and protein-coding gene mRNAs. The majority of small RNAs derived from repetitive elements and lncRNAs exhibited typical piRNAs features. By contrast, majority of protein-coding gene-derived 24-32 nt small RNAs lack the hallmarks of piRNAs and have signatures of nontemplated 3' end tailing. Most of the atypical small RNAs exhibit female-biased expression and originate from mitochondrial and nuclear genes involved in energy metabolism. We also identified atypical genic small RNAs in <i>Anopheles gambiae</i> somatic tissues, which further validates the noncanonical mechanism of their production. We discuss a novel mechanism of small RNA production in mosquito somatic tissues and the possible functional significance of genic small RNAs.</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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365764","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: 2025-01-05DOI: 10.1080/15476286.2024.2448387
Lei Chen, Xia Gao, Xiangshen Liu, Ye Zhu, Dong Wang
{"title":"Translational regulation of PKD1 by evolutionarily conserved upstream open reading frames.","authors":"Lei Chen, Xia Gao, Xiangshen Liu, Ye Zhu, Dong Wang","doi":"10.1080/15476286.2024.2448387","DOIUrl":"10.1080/15476286.2024.2448387","url":null,"abstract":"<p><p>Mutations in <i>PKD1</i> coding sequence and abnormal PKD1 expression levels contribute to the development of autosomal-dominant polycystic kidney disease, the most common genetic disorder. Regulation of PKD1 expression by factors located in the promoter and 3´ UTR have been extensively studied. Less is known about its regulation by 5´ UTR elements. In this study, we investigated the effects of uORFs and uORF-affecting variants by combining bioinformatic analyses, luciferase reporter assays, RT-qPCR and immunoblotting experiments. Our analyses demonstrate that <i>PKD1</i> mRNA contains two evolutionarily conserved translation-inhibitory uORFs. uORF1 is translatable, and uORF2 is likely not translatable. The 5´ UTR and uORFs do not modulate downstream protein output under endoplasmic reticulum stress and oxidative stress conditions. Some of uORF-perturbing variants in the SNP database are predicted to affect gene translation. Luciferase reporter assays and RT-qPCR results reveal that rs2092942382 and rs1596636969 increase, while rs2092942900 decreases main gene translation without affecting transcription. Antisense oligos targeting the uORFs reduce luciferase protein levels without altering luciferase mRNA levels. Our results establish <i>PKD1</i> as a novel target of uORF-mediated translational regulation and mutations that perturb uORFs may dysregulate PKD1 protein level.</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/PMC11810096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932624","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: 2025-03-12DOI: 10.1080/15476286.2025.2475421
Bingning Xie, Ann Dean
{"title":"Noncoding function of super enhancer derived <i>Cpox</i> pre-mRNA in modulating neighbouring gene expression and chromatin interactions.","authors":"Bingning Xie, Ann Dean","doi":"10.1080/15476286.2025.2475421","DOIUrl":"10.1080/15476286.2025.2475421","url":null,"abstract":"<p><p>Super enhancers are important regulators of gene expression that often overlap with protein-coding genes. However, it is unclear whether the overlapping protein-coding genes and the RNA derived from them contribute to enhancer activity. Using an erythroid-specific super enhancer that overlaps the <i>Cpox</i> gene as a model, <i>Cpox</i> pre-mRNA is found to have a non-coding function in regulating neighbouring protein-coding genes, eRNA expression and TAD interactions. Depletion of <i>Cpox</i> pre-mRNA leads to accumulation of H3K27me3 and release of p300 from the <i>Cpox</i> locus, activating an intra-TAD enhancer and gene expression. Additionally, a head-to-tail interaction between the TAD boundary genes <i>Cpox</i> and <i>Dcbld2</i> is identified, facilitated by a novel type of repressive loop anchored by p300 and PRC2/H3K27me3. These results uncover a regulatory role for pre-mRNA transcribed within a super enhancer context and provide insight into head-to-tail inter-gene interaction in the regulation of gene expression and oncogene activation.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-17"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573926","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: 2025-02-27DOI: 10.1080/15476286.2025.2470511
Jennifer Jungfleisch, Fátima Gebauer
{"title":"RNA-binding proteins as therapeutic targets in cancer.","authors":"Jennifer Jungfleisch, Fátima Gebauer","doi":"10.1080/15476286.2025.2470511","DOIUrl":"10.1080/15476286.2025.2470511","url":null,"abstract":"<p><p>RNA-binding proteins (RBPs) have emerged as critical regulators of cancer progression, influencing virtually all hallmarks of cancer. Their ability to modulate gene expression patterns that promote or inhibit tumorigenesis has positioned RBPs as promising targets for novel anti-cancer therapies. This mini-review summarizes the current state of RBP-targeted cancer treatments, focusing on five examples, eIF4F, FTO, SF3B1, RBM39 and nucleolin. We highlight the diversity of current targeting approaches and discuss ongoing challenges including the complexity of RBP regulatory networks, potential off-target effects and the need for more specific targeting methods. By assessing the future potential of novel therapeutic avenues, we provide insights into the evolving landscape of cancer treatment and the critical role RBPs may play in next-generation therapeutics.</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/PMC11869776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524272","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 : 2025-03-14DOI: 10.1080/15476286.2025.2478539
Lei Ji, Youguo Chen, Xiaoping Chen
{"title":"Circular RNA Circ_0002762 promotes cell migration and invasion in cervical squamous cell carcinoma via activating RelA/nuclear factor kappa B (nf-kB) signaling pathway.","authors":"Lei Ji, Youguo Chen, Xiaoping Chen","doi":"10.1080/15476286.2025.2478539","DOIUrl":"https://doi.org/10.1080/15476286.2025.2478539","url":null,"abstract":"<p><p>Cervical cancer is a leading cause of cancer-related deaths, with cervical squamous cell carcinoma (CSCC) accounting for a majority of cases. Circular RNAs (circRNAs) have been repeatedly suggested as crucial effectors in modulating development of multiple malignancies. The expression of circ_0002762 was predicted to be high in CSCC tissues in GEO dataset, but the functional role and underlying regulatory mechanism of circ_0002762 in CSCC was unclear. By series of functional assays and mechanism assays, supported by bioinformatics analysis, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis and western blot assays, we identified that circ_0002762 aberrantly up-regulated in CSCC, promoted CSCC cell migration and invasion. Mechanically, circ_0002762 was transcriptionally activated by Fork head box A1 (FOXA1). Moreover, the involvement of nuclear factor kappa B (NF-kB) signalling in circ_0002762 regulation mechanism in CSCC cells was ascertained. Additionally, circ_0002762, predominantly accumulated in cell cytoplasm, was proved to recruit Mov10 RISC complex RNA helicase (MOV10) to enhance RelA mRNA stability, thus affecting CSCC cell migration and invasion. In summary, FOXA1-mediated circ_0002762 up-regulation could enhance the migratory and invasive abilities of CSCC cells via the MOV10/RelA/NF-kB pathway.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625775","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":"Elav/hu RNA-Binding protein family: key regulators in neurological disorders, cancer, and other diseases.","authors":"Huxitaer Wutikeli, Ting Xie, Wenjun Xiong, Yin Shen","doi":"10.1080/15476286.2025.2471133","DOIUrl":"https://doi.org/10.1080/15476286.2025.2471133","url":null,"abstract":"<p><p>The ELAV/Hu family represents a crucial group of RNA-binding proteins predominantly expressed in neurons, playing significant roles in mRNA transcription and translation. These proteins bind to AU-rich elements in transcripts to regulate the expression of cytokines, growth factors, and the development and maintenance of neurons. Elav-like RNA-binding proteins exhibit remarkable molecular weight conservation across different species, highlighting their evolutionary conservation. Although these proteins are widely expressed in the nervous system and other cell types, variations in the DNA sequences of the four Elav proteins contribute to their distinct roles in neurological disorders, cancer, and other Diseases . Elavl1, a ubiquitously expressed family member, is integral to processes such as cell growth, ageing, tumorigenesis, and inflammatory diseases. Elavl2, primarily expressed in the nervous and reproductive systems, is critical for central nervous system and retinal development; its dysregulation has been implicated in neurodevelopmental disorders such as autism. Both Elavl3 and Elavl4 are restricted to the nervous system and are involved in neuronal differentiation and excitability. Elavl3 is essential for cerebellar function and has been associated with epilepsy, while Elavl4 is linked to neurodegenerative diseases, including Parkinson's and Alzheimer's diseases. This paper provides a comprehensive review of the ELAV/Hu family's role in nervous system development, neurological disorders, cancer, and other diseases.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503664","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":"An orthology-based methodology as a complementary approach to retrieve evolutionarily conserved A-to-I RNA editing sites.","authors":"Jiyao Liu,Tianyou Zhao,Caiqing Zheng,Ling Ma,Fan Song,Li Tian,Wanzhi Cai,Hu Li,Yuange Duan","doi":"10.1080/15476286.2024.2397757","DOIUrl":"https://doi.org/10.1080/15476286.2024.2397757","url":null,"abstract":"Adar-mediated adenosine-to-inosine (A-to-I) mRNA editing is a conserved mechanism that exerts diverse regulatory functions during the development, evolution, and adaptation of metazoans. The accurate detection of RNA editing sites helps us understand their biological significance. In this work, with an improved genome assembly of honeybee (Apis mellifera), we used a new orthology-based methodology to complement the traditional pipeline of (de novo) RNA editing detection. Compared to the outcome of traditional pipeline, we retrieved many novel editing sites in CDS that are deeply conserved between honeybee and other distantly related insects. The newly retrieved sites were missed by the traditional de novo identification due to the stringent criteria for controlling false-positive rate. Caste-specific editing sites are identified, including an Ile>Met auto-recoding site in Adar. This recoding was even conserved between honeybee and bumblebee, suggesting its putative regulatory role in shaping the phenotypic plasticity of eusocial Hymenoptera. In summary, we proposed a complementary approach to the traditional pipeline and retrieved several previously unnoticed CDS editing sites. From both technical and biological aspects, our works facilitate future researches on finding the functional editing sites and advance our understanding on the connection between RNA editing and the great phenotypic diversity of organisms.","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"29-45"},"PeriodicalIF":4.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142193451","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 : 2024-09-10DOI: 10.1080/15476286.2024.2395718
Andre Brezski,Justin Murtagh,Marcel H Schulz,Kathi Zarnack
{"title":"A systematic analysis of circRNAs in subnuclear compartments.","authors":"Andre Brezski,Justin Murtagh,Marcel H Schulz,Kathi Zarnack","doi":"10.1080/15476286.2024.2395718","DOIUrl":"https://doi.org/10.1080/15476286.2024.2395718","url":null,"abstract":"CircRNAs are an important class of RNAs with diverse cellular functions in human physiology and disease. A thorough knowledge of circRNAs including their biogenesis and subcellular distribution is important to understand their roles in a wide variety of processes. However, the analysis of circRNAs from total RNA sequencing data remains challenging. Therefore, we developed Calcifer, a versatile workflow for circRNA annotation. Using Calcifer, we analysed APEX-Seq data to compare circRNA occurrence between whole cells, nucleus and subnuclear compartments. We generally find that circRNAs show higher abundance in whole cells compared to nuclear samples, consistent with their accumulation in the cytoplasm. The notable exception is the single-exon circRNA circCANX(9), which is unexpectedly enriched in the nucleus. In addition, we observe that circFIRRE prevails over the linear lncRNA FIRRE in both the cytoplasm and the nucleus. Zooming in on the subnuclear compartments, we show that circRNAs are strongly depleted from nuclear speckles, indicating that excess splicing factors in this compartment counteract back-splicing. Our results thereby provide valuable insights into the subnuclear distribution of circRNAs. Regarding circRNA function, we surprisingly find that the majority of all detected circRNAs possess complete open reading frames with potential for cap-independent translation. Overall, we show that Calcifer is an easy-to-use, versatile and sustainable workflow for the annotation of circRNAs which expands the repertoire of circRNA tools and allows to gain new insights into circRNA distribution and function.","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"77 1","pages":"1-16"},"PeriodicalIF":4.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142193452","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":"Silencing LINC00663 inhibits inflammation and angiogenesis through downregulation of NR2F1 via EBF1 in bladder cancer","authors":"Xiulong Zhong, Lijiang Sun, Junxiang Liu, Xiaokun Yang, Minghui Hou, Xinning Wang, Huifeng Diao","doi":"10.1080/15476286.2024.2368304","DOIUrl":"https://doi.org/10.1080/15476286.2024.2368304","url":null,"abstract":"This study is to elucidate the effect of the LINC00663/EBF1/NR2F1 axis on inflammation and angiogenesis in bladder cancer (BC) and related molecular mechanisms. After transfection, functional exper...","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"77 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141550256","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 : 2024-04-17DOI: 10.1080/15476286.2024.2340297
Josephine Davey-Young, Farah Hasan, Rasangi Tennakoon, Peter Rozik, Henry Moore, Peter Hall, Ecaterina Cozma, Julie Genereaux, Kyle S. Hoffman, Patricia P. Chan, Todd M. Lowe, Christopher J. Brandl, Patrick O’Donoghue
{"title":"Mistranslating the genetic code with leucine in yeast and mammalian cells","authors":"Josephine Davey-Young, Farah Hasan, Rasangi Tennakoon, Peter Rozik, Henry Moore, Peter Hall, Ecaterina Cozma, Julie Genereaux, Kyle S. Hoffman, Patricia P. Chan, Todd M. Lowe, Christopher J. Brandl, Patrick O’Donoghue","doi":"10.1080/15476286.2024.2340297","DOIUrl":"https://doi.org/10.1080/15476286.2024.2340297","url":null,"abstract":"Translation fidelity relies on accurate aminoacylation of transfer RNAs (tRNAs) by aminoacyl-tRNA synthetases (AARSs). AARSs specific for alanine (Ala), leucine (Leu), serine, and pyrrolysine do no...","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"12 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617406","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}