RNA Biology最新文献_第3页

RNase P cleavage of pseudoknot substrates reveals differences in active site architecture that depend on residue N-1 in the 5' leader. 伪结底物的RNase P切割揭示了活性位点结构的差异，这取决于5'先导物中的残基N-1。

IF 3.6 3区生物学

RNA Biology Pub Date : 2025-12-01 Epub Date: 2025-01-20 DOI: 10.1080/15476286.2024.2427906

David M Kosek, J Luis Leal, Ema Kikovska-Stojanovska, Guanzhong Mao, Shiying Wu, Samuel C Flores, Leif A Kirsebom

{"title":"RNase P cleavage of pseudoknot substrates reveals differences in active site architecture that depend on residue N-1 in the 5' leader.","authors":"David M Kosek, J Luis Leal, Ema Kikovska-Stojanovska, Guanzhong Mao, Shiying Wu, Samuel C Flores, Leif A Kirsebom","doi":"10.1080/15476286.2024.2427906","DOIUrl":"https://doi.org/10.1080/15476286.2024.2427906","url":null,"abstract":"We show that a small biotin-binding RNA aptamer that folds into a pseudoknot structure acts as a substrate for bacterial RNase P RNA (RPR) with and without the RNase P C5 protein. Cleavage in the single-stranded region in loop 1 was shown to depend on the presence of a RCCA-motif at the 3' end of the substrate. The nucleobase and the 2'hydroxyl at the position immediately 5' of the cleavage site contribute to both cleavage efficiency and site selection, where C at this position induces significant cleavage at an alternative site, one base upstream of the main cleavage site. The frequencies of cleavage at these two sites and Mg2+ binding change upon altering the structural topology in the vicinity of the cleavage site as well as by replacing Mg2+ with other divalent metal ions. Modelling studies of RPR in complex with the pseudoknot substrates suggest alternative structural topologies for cleavage at the main and the alternative site and a shift in positioning of Mg2+ that activates the H2O nucleophile. Together, our data are consistent with a model where the organization of the active site structure and positioning of Mg2+ is influenced by the identities of residues at and in the vicinity of the site of cleavage.","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-19"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010860","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}

引用次数: 0

The role and function of lncRNA in ageing-associated liver diseases. lncRNA在衰老相关肝脏疾病中的作用和功能

IF 3.6 3区生物学

RNA Biology Pub Date : 2025-12-01 Epub Date: 2024-12-19 DOI: 10.1080/15476286.2024.2440678

Peyman Kheirandish Zarandi, Mohsen Ghiasi, Mohammad Heiat

{"title":"The role and function of lncRNA in ageing-associated liver diseases.","authors":"Peyman Kheirandish Zarandi, Mohsen Ghiasi, Mohammad Heiat","doi":"10.1080/15476286.2024.2440678","DOIUrl":"10.1080/15476286.2024.2440678","url":null,"abstract":"Liver diseases are a significant global health issue, characterized by elevated levels of disorder and death. The substantial impact of ageing on liver diseases and their prognosis is evident. Multiple processes are involved in the ageing process, which ultimately leads to functional deterioration of this organ. The process of liver ageing not only renders the liver more susceptible to diseases but also compromises the integrity of other organs due to the liver's critical function in metabolism regulation. A growing body of research suggests that long non-coding RNAs (lncRNAs) play a significant role in the majority of pathophysiological pathways. They regulate gene expression through a variety of interactions with microRNAs (miRNAs), messenger RNAs (mRNAs), DNA, or proteins. LncRNAs exert a major influence on the progression of age-related liver diseases through the regulation of cell proliferation, necrosis, apoptosis, senescence, and metabolic reprogramming. A concise overview of the current understanding of lncRNAs and their potential impact on the development of age-related liver diseases will be provided in this mini-review.","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/PMC11660375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855134","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}

引用次数: 0

Two complementing in vivo selection systems based on CCA-trimming exonucleases as a tool to monitor, select and evaluate enzymatic features of tRNA nucleotidyltransferases. 基于cca修饰外切酶的两种互补的体内选择系统，作为监测、选择和评估tRNA核苷酸转移酶酶学特征的工具。

IF 3.6 3区生物学

RNA Biology Pub Date : 2025-12-01 Epub Date: 2025-01-29 DOI: 10.1080/15476286.2025.2453963

Karolin Wellner, Josefine Gnauck, Dorian Bernier, Stephan H Bernhart, Heike Betat, Mario Mörl

{"title":"Two complementing in vivo selection systems based on CCA-trimming exonucleases as a tool to monitor, select and evaluate enzymatic features of tRNA nucleotidyltransferases.","authors":"Karolin Wellner, Josefine Gnauck, Dorian Bernier, Stephan H Bernhart, Heike Betat, Mario Mörl","doi":"10.1080/15476286.2025.2453963","DOIUrl":"10.1080/15476286.2025.2453963","url":null,"abstract":"tRNA nucleotidyltransferase represents a ubiquitous and essential activity that adds the indispensable CCA triplet to the 3'-end of tRNAs. To fulfill this function, the enzyme contains a set of highly conserved motifs whose coordinated interplay is crucial for the sequence-specific CCA polymerization. In the human enzyme, alterations within these regions have been shown to lead to the manifestation of disease. Recently, we developed an in vivo screening system that allows for the selection and analysis of tRNA nucleotidyltransferase variants by challenging terminal AMP incorporation into tRNA during induced RNase T-catalyzed CCA-decay. Here, we extend this method for screening of full CCA-end repair by utilizing the CCA-trimming activity of exonuclease LCCR4. To demonstrate the combined potential of these two in vivo selection systems, we applied a semi-rational library design to investigate the mode of operation of catalytically important motifs in the human CCA-adding enzyme. This approach revealed unexpected requirements for amino acid composition in two motifs and gives new insights into the mechanism of CCA addition. The data show the potential of these RNase-based screening systems, as they allow the detection of enzyme variations that would not have been identified by a conventional rational approach. Furthermore, the combination of both RNase T and LCCR4 systems can be used to investigate and dissect the effects of pathogenic mutations on C- and A-addition.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010861","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}

引用次数: 0

Characterization of the binding features between SARS-CoV-2 5'-proximal transcripts of genomic RNA and nucleocapsid proteins.

IF 3.6 3区生物学

RNA Biology Pub Date : 2025-12-01 Epub Date: 2025-03-12 DOI: 10.1080/15476286.2025.2471643

Shih-Cheng Chen, Cui-Ting Xu, Chuan-Fu Chang, Chia-Shin Yang, Pin-Han Lin, Wei-Min Liu, Yeh Chen, Chien-Hung Yu

{"title":"Characterization of the binding features between SARS-CoV-2 5'-proximal transcripts of genomic RNA and nucleocapsid proteins.","authors":"Shih-Cheng Chen, Cui-Ting Xu, Chuan-Fu Chang, Chia-Shin Yang, Pin-Han Lin, Wei-Min Liu, Yeh Chen, Chien-Hung Yu","doi":"10.1080/15476286.2025.2471643","DOIUrl":"10.1080/15476286.2025.2471643","url":null,"abstract":"Packaging signals (PSs) of coronaviruses (CoVs) are specific RNA elements recognized by nucleocapsid (N) proteins that direct the selective packaging of genomic RNAs (gRNAs). These signals have been identified in the coding regions of the nonstructural protein 15 (Nsp 15) in CoVs classified under Embecovirus, a subgenus of betacoronaviruses (beta-CoVs). The PSs in other alpha- and beta-CoVs have been proposed to reside in the 5'-proximal regions of gRNAs, supported by comprehensive phylogenetic evidence. However, experimental data remain limited. In this study, we investigated the interactions between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) 5'-proximal gRNA transcripts and N proteins using electrophoretic mobility shift assays (EMSAs). Our findings revealed that the in vitro synthesized 5'-proximal gRNA transcripts of CoVs can shift from a major conformation to alternative conformations. We also observed that the conformer comprising multiple stem-loops (SLs) is preferentially bound by N proteins. Deletions of the 5'-proximal structural elements of CoV gRNA transcripts, SL1 and SL5a/b/c in particular, were found to promote the formation of alternative conformations. Furthermore, we identified RNA-binding peptides from a pool derived from SARS-CoV N protein. These RNA-interacting peptides were shown to preferentially bind to wild-type SL5a RNA. In addition, our observations of N protein condensate formation in vitro demonstrated that liquid-liquid phase separation (LLPS) of N proteins with CoV-5'-UTR transcripts was influenced by the presence of SL5a/b/c. In conclusion, these results collectively reveal previously uncharacterized binding features between the 5'-proximal transcripts of CoV gRNAs and N proteins.","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","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/PMC11913385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617012","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}

引用次数: 0

ELAV/Hu RNA-binding protein family: key regulators in neurological disorders, cancer, and other diseases. Elav/hu RNA 结合蛋白家族：神经系统疾病、癌症和其他疾病的关键调节因子。

IF 3.6 3区生物学

RNA Biology Pub Date : 2025-12-01 Epub Date: 2025-03-20 DOI: 10.1080/15476286.2025.2471133

Huxitaer Wutikeli, Ting Xie, Wenjun Xiong, Yin Shen

{"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":"10.1080/15476286.2025.2471133","url":null,"abstract":"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.","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/PMC11926907/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analysis of somatic piRNAs in the malaria mosquito Anopheles coluzzii reveals atypical classes of genic small RNAs.

IF 3.6 3区生物学

RNA Biology Pub Date : 2025-12-01 Epub Date: 2025-02-16 DOI: 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 Anopheles coluzzii 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":"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 Anopheles coluzzii 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 Anopheles gambiae 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.","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}

引用次数: 0

Translational regulation of PKD1 by evolutionarily conserved upstream open reading frames. 进化保守的上游开放阅读框对PKD1的翻译调控。

IF 3.6 3区生物学

RNA Biology Pub Date : 2025-12-01 Epub Date: 2025-01-05 DOI: 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":"Mutations in PKD1 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 PKD1 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 PKD1 as a novel target of uORF-mediated translational regulation and mutations that perturb uORFs may dysregulate PKD1 protein level.","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}

引用次数: 0

Noncoding function of super enhancer derived Cpox pre-mRNA in modulating neighbouring gene expression and chromatin interactions.

IF 3.6 3区生物学

RNA Biology Pub Date : 2025-12-01 Epub Date: 2025-03-12 DOI: 10.1080/15476286.2025.2475421

Bingning Xie, Ann Dean

引用次数: 0

RNA-binding proteins as therapeutic targets in cancer.

IF 3.6 3区生物学

RNA Biology Pub Date : 2025-12-01 Epub Date: 2025-02-27 DOI: 10.1080/15476286.2025.2470511

Jennifer Jungfleisch, Fátima Gebauer

引用次数: 0

Wide-spectrum profiling of plasma cell-free RNA and the potential for health-monitoring.

IF 3.6 3区生物学

RNA Biology Pub Date : 2025-12-01 Epub Date: 2025-03-31 DOI: 10.1080/15476286.2025.2481736

Xinxin Wang, Shaogang Li, Rijing Ou, Wending Pang, Yingying Wang, Yifan Zhang, Yu Lin, Changlin Yang, Wei Chen, Changgui Lei, Guodan Zeng, Wenwen Zhou, Yeqin Wang, Jianhua Yin, Haiqiang Zhang, Xin Jin, Yan Zhang

{"title":"Wide-spectrum profiling of plasma cell-free RNA and the potential for health-monitoring.","authors":"Xinxin Wang, Shaogang Li, Rijing Ou, Wending Pang, Yingying Wang, Yifan Zhang, Yu Lin, Changlin Yang, Wei Chen, Changgui Lei, Guodan Zeng, Wenwen Zhou, Yeqin Wang, Jianhua Yin, Haiqiang Zhang, Xin Jin, Yan Zhang","doi":"10.1080/15476286.2025.2481736","DOIUrl":"10.1080/15476286.2025.2481736","url":null,"abstract":"Circulating cell-free RNA (cfRNA) has emerged as a promising analyte for disease detection. However, the comprehensive profiling of diverse cfRNA types remains under-characterized. Here, we applied a new wide-spectrum cfRNA sequencing method and simultaneously captured rRNA, tRNA, mRNA, miRNA, lncRNA and all mitochondrial RNA. The cfRNA compositions, size distributions and highly abundant cfRNA genes were analysed for each type of cfRNA. We depicted the cfRNA cell types of origin profiles of 66 generally healthy individuals and found that BMI showed a significant impact on the kidney-derived cfRNA proportion. Three individuals with some liver problems were identified because of relatively high levels of hepatocyte-specific cfRNA. The abundance levels of different genes and RNA types, including mRNA, miRNA and lncRNA, were significantly correlated with the liver function test results. The genes of individual cfRNA variances were enriched in pathways associated with common diseases such as liver diseases, virus infections, cancers and metabolic diseases. This study provided a profiling of cfRNA and displayed the potential of cfRNA as a biomarker in health monitoring.","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","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":"143664462","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}

引用次数: 0