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Temperature-sensing riboceptors. 温度感应核糖受体
IF 3.6 3区 生物学
RNA Biology Pub Date : 2024-01-01 Epub Date: 2024-07-17 DOI: 10.1080/15476286.2024.2379118
Savani Anbalagan
{"title":"Temperature-sensing riboceptors.","authors":"Savani Anbalagan","doi":"10.1080/15476286.2024.2379118","DOIUrl":"10.1080/15476286.2024.2379118","url":null,"abstract":"<p><p>Understanding how cells sense temperature is a fundamental question in biology and is pivotal for the evolution of life. In numerous organisms, temperature is not only sensed but also generated due to cellular processes. Consequently, the mechanisms governing temperature sensation in various organisms have been experimentally elucidated. Extending upon others' proposals and demonstration of protein- and nucleic acid-based thermosensors, and utilizing a colonial India 'punkah-wallahs' analogy, I present my rationale for the necessity of temperature sensing in every organelle in a cell. Finally, I propose temperature-sensing <b>riboceptors</b> (<b>ribo</b>nucleic acid re<b>ceptors</b>) to integrate all the RNA molecules (mRNA, non-coding RNA, and so forth) capable of sensing temperature and triggering a signaling event, which I call as thermocrine signaling. This approach could enable the identification of riboceptors in every cell of almost every organism, not only for temperature but also for other classes of ligands, including gaseous solutes, and water.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11259075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627578","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
Poly(G)7 box: a functional element of mammalian 18S rRNA involved in translation. Poly(G)7 box:哺乳动物 18S rRNA 中参与翻译的一个功能元件。
IF 3.6 3区 生物学
RNA Biology Pub Date : 2024-01-01 Epub Date: 2024-09-05 DOI: 10.1080/15476286.2024.2399310
Dahao Wei, Zhangyu Mai, Xinan Li, Tianli Yu, Jiangchao Li
{"title":"Poly(G)<sub>7</sub> box: a functional element of mammalian 18S rRNA involved in translation.","authors":"Dahao Wei, Zhangyu Mai, Xinan Li, Tianli Yu, Jiangchao Li","doi":"10.1080/15476286.2024.2399310","DOIUrl":"https://doi.org/10.1080/15476286.2024.2399310","url":null,"abstract":"<p><p>In eukaryotes, the ribosomal small subunit (40S) is composed of 18S rRNA and 33 ribosomal proteins. 18S rRNA has a special secondary structure and is an indispensable part of the translation process. Herein, a special sequence located in mammalian 18S rRNA named Poly(G)<sub>7</sub>box, which is composed of seven guanines, was found. Poly(G)<sub>7</sub> can form a special and stable secondary structure by binding to the translation elongation factor subunit eEF1D and the ribosomal protein RPL32. Poly(G)<sub>7</sub>box was transfected into cells, and the translation efficiency of cells was inhibited. We believe that Poly(G)<sub>7</sub>box is an important translation-related functional element located on mammalian 18S rRNA, meanwhile the Poly(G)<sub>7</sub> located on mRNA 5' and 3' box does not affect mRNA translation.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133613","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
Assessment of different enrichment methods revealed the optimal approach to identify bovine circRnas. 对不同富集方法的评估揭示了识别牛 circRnas 的最佳方法。
IF 4.1 3区 生物学
RNA Biology Pub Date : 2024-01-01 Epub Date: 2024-05-26 DOI: 10.1080/15476286.2024.2356334
Yixin Wang, Jian Wang, Robert J Gruninger, Tim A McAllister, Mingzhou Li, Le Luo Guan
{"title":"Assessment of different enrichment methods revealed the optimal approach to identify bovine circRnas.","authors":"Yixin Wang, Jian Wang, Robert J Gruninger, Tim A McAllister, Mingzhou Li, Le Luo Guan","doi":"10.1080/15476286.2024.2356334","DOIUrl":"10.1080/15476286.2024.2356334","url":null,"abstract":"<p><p>Although circular RNAs (circRNAs) play important roles in regulating gene expression, the understanding of circRNAs in livestock animals is scarce due to the significant challenge to characterize them from a biological sample. In this study, we assessed the outcomes of bovine circRNA identification using six enrichment approaches with the combination of ribosomal RNAs removal (<b>Ribo</b>); linear RNAs degradation (<b>R</b>); linear RNAs and RNAs with structured 3' ends degradation (<b>RTP</b>); ribosomal RNAs coupled with linear RNAs elimination (<b>Ribo-R</b>); ribosomal RNA, linear RNAs and RNAs with poly (A) tailing elimination (<b>Ribo-RP</b>); and ribosomal RNA, linear RNAs and RNAs with structured 3' ends elimination (<b>Ribo-RTP</b>), respectively. RNA-sequencing analysis revealed that different approaches led to varied ratio of uniquely mapped reads, false-positive rate of identifying circRNAs, and the number of circRNAs per million clean reads (<i>P</i><sub><i>adj</i></sub> <0.05). Out of 2,285 and 2,939 highly confident circRNAs identified in liver and rumen tissues, respectively, 308 and 260 were commonly identified from five methods, with Ribo-RTP method identified the highest number of circRNAs. Besides, 507 of 4,051 identified bovine highly confident circRNAs had shared splicing sites with human circRNAs. The findings from this work provide optimized methods to identify bovine circRNAs from cattle tissues for downstream research of their biological roles in cattle.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11135877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155378","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
The catalytic activity of methyltransferase METTL15 is dispensable for its role in mitochondrial ribosome biogenesis. 甲基转移酶 METTL15 在线粒体核糖体生物发生过程中的作用离不开其催化活性。
IF 3.6 3区 生物学
RNA Biology Pub Date : 2024-01-01 Epub Date: 2024-06-24 DOI: 10.1080/15476286.2024.2369374
Christian D Mutti, Lindsey Van Haute, Michal Minczuk
{"title":"The catalytic activity of methyltransferase METTL15 is dispensable for its role in mitochondrial ribosome biogenesis.","authors":"Christian D Mutti, Lindsey Van Haute, Michal Minczuk","doi":"10.1080/15476286.2024.2369374","DOIUrl":"10.1080/15476286.2024.2369374","url":null,"abstract":"<p><p>Ribosomes are large macromolecular complexes composed of both proteins and RNA, that require a plethora of factors and post-transcriptional modifications for their biogenesis. In human mitochondria, the ribosomal RNA is post-transcriptionally modified at ten sites. The N4-methylcytidine (m<sup>4</sup>C) methyltransferase, METTL15, modifies the 12S rRNA of the small subunit at position C1486. The enzyme is essential for mitochondrial protein synthesis and assembly of the mitoribosome small subunit, as shown here and by previous studies. Here, we demonstrate that the m<sup>4</sup>C modification is not required for small subunit biogenesis, indicating that the chaperone-like activity of the METTL15 protein itself is an essential component for mitoribosome biogenesis.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11197891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446915","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
Small molecule inhibition of RNA binding proteins in haematologic cancer. 小分子抑制血液肿瘤中的 RNA 结合蛋白。
IF 4.1 3区 生物学
RNA Biology Pub Date : 2024-01-01 Epub Date: 2024-02-08 DOI: 10.1080/15476286.2024.2303558
Amit K Jaiswal, Michelle L Thaxton, Georgia M Scherer, Jacob P Sorrentino, Neil K Garg, Dinesh S Rao
{"title":"Small molecule inhibition of RNA binding proteins in haematologic cancer.","authors":"Amit K Jaiswal, Michelle L Thaxton, Georgia M Scherer, Jacob P Sorrentino, Neil K Garg, Dinesh S Rao","doi":"10.1080/15476286.2024.2303558","DOIUrl":"10.1080/15476286.2024.2303558","url":null,"abstract":"<p><p>In recent years, advances in biomedicine have revealed an important role for post-transcriptional mechanisms of gene expression regulation in pathologic conditions. In cancer in general and leukaemia specifically, RNA binding proteins have emerged as important regulator of RNA homoeostasis that are often dysregulated in the disease state. Having established the importance of these pathogenetic mechanisms, there have been a number of efforts to target RNA binding proteins using oligonucleotide-based strategies, as well as with small organic molecules. The field is at an exciting inflection point with the convergence of biomedical knowledge, small molecule screening strategies and improved chemical methods for synthesis and construction of sophisticated small molecules. Here, we review the mechanisms of post-transcriptional gene regulation, specifically in leukaemia, current small-molecule based efforts to target RNA binding proteins, and future prospects.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10857685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703226","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
Endogenous ZAP affects Zika virus RNA interactome. 内源性 ZAP 影响寨卡病毒 RNA 交互组。
IF 3.6 3区 生物学
RNA Biology Pub Date : 2024-01-01 Epub Date: 2024-08-25 DOI: 10.1080/15476286.2024.2388911
Ahmad Jawad Sabir, Nguyen Phuong Khanh Le, Prince Pal Singh, Uladzimir Karniychuk
{"title":"Endogenous ZAP affects Zika virus RNA interactome.","authors":"Ahmad Jawad Sabir, Nguyen Phuong Khanh Le, Prince Pal Singh, Uladzimir Karniychuk","doi":"10.1080/15476286.2024.2388911","DOIUrl":"10.1080/15476286.2024.2388911","url":null,"abstract":"<p><p>One of the most recent advances in the analysis of viral RNA-cellular protein interactions is the Comprehensive Identification of RNA-binding Proteins by Mass Spectrometry (ChIRP-MS). Here, we used ChIRP-MS in mock-infected and Zika-infected wild-type cells and cells knockout for the zinc finger CCCH-type antiviral protein 1 (ZAP). We characterized 'ZAP-independent' and 'ZAP-dependent' cellular protein interactomes associated with flavivirus RNA and found that ZAP affects cellular proteins associated with Zika virus RNA. The ZAP-dependent interactome identified with ChIRP-MS provides potential ZAP co-factors for antiviral activity against Zika virus and possibly other viruses. Identifying the full spectrum of ZAP co-factors and mechanisms of how they act will be critical to understanding the ZAP antiviral system and may contribute to the development of antivirals.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056347","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
Post-transcriptional capping generates coenzyme A-linked RNA. 转录后封顶产生辅酶a连接RNA。
IF 4.1 3区 生物学
RNA Biology Pub Date : 2024-01-01 Epub Date: 2023-11-30 DOI: 10.1080/15476286.2023.2288740
Krishna Sapkota, Jordyn K Lucas, Jarrett W Faulkner, Matt F Lichte, Yan-Lin Guo, Donald H Burke, Faqing Huang
{"title":"Post-transcriptional capping generates coenzyme A-linked RNA.","authors":"Krishna Sapkota, Jordyn K Lucas, Jarrett W Faulkner, Matt F Lichte, Yan-Lin Guo, Donald H Burke, Faqing Huang","doi":"10.1080/15476286.2023.2288740","DOIUrl":"10.1080/15476286.2023.2288740","url":null,"abstract":"<p><p>NAD can be inserted co-transcriptionally via non-canonical initiation to form NAD-RNA. However, that mechanism is unlikely for CoA-linked RNAs due to low intracellular concentration of the required initiator nucleotide, 3'-dephospho-CoA (dpCoA). We report here that phosphopantetheine adenylyltransferase (PPAT), an enzyme of CoA biosynthetic pathway, accepts RNA transcripts as its acceptor substrate and transfers 4'-phosphopantetheine to yield CoA-RNA post-transcriptionally. Synthetic natural (RNAI) and small artificial RNAs were used to identify the features of RNA that are needed for it to serve as PPAT substrate. RNAs with 4-10 unpaired nucleotides at the 5' terminus served as PPAT substrates, but RNAs having <4 unpaired nucleotides did not undergo capping. No capping was observed when the +1A was changed to G or when 5' triphosphate was removed by RNA pyrophosphohydrolase (RppH), suggesting the enzyme recognizes pppA-RNA as an ATP analog. PPAT binding affinities were equivalent for transcripts with +1A, +1 G, or 5'OH (+1A), indicating that productive enzymatic recognition is driven more by local positioning effects than by overall binding affinity. Capping rates were independent of the number of unpaired nucleotides in the range of 4-10 nucleotides. Capping was strongly inhibited by ATP, reducing CoA-RNA production ~70% when equimolar ATP and substrate RNA were present. Dual bacterial expression of candidate RNAs with different 5' structures followed by CoA-RNA CaptureSeq revealed 12-fold enrichment of the better PPAT substrate, consistent with <i>in vivo</i> CoA-capping of RNA transcripts by PPAT. These results suggest post-transcriptional RNA capping as a possible mechanism for the biogenesis of CoA-RNAs in bacteria.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462396","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
Circular RNAs in non-alcoholic fatty liver disease: Functions and clinical significance. 非酒精性脂肪肝中的环状 RNA:功能和临床意义
IF 4.1 3区 生物学
RNA Biology Pub Date : 2024-01-01 Epub Date: 2023-12-19 DOI: 10.1080/15476286.2023.2290769
Qingmin Zeng, Chang-Hai Liu, Javier Ampuero, Dongbo Wu, Wei Jiang, Lingyun Zhou, Hong Li, Lang Bai, Manuel Romero-Gómez, Hong Tang
{"title":"Circular RNAs in non-alcoholic fatty liver disease: Functions and clinical significance.","authors":"Qingmin Zeng, Chang-Hai Liu, Javier Ampuero, Dongbo Wu, Wei Jiang, Lingyun Zhou, Hong Li, Lang Bai, Manuel Romero-Gómez, Hong Tang","doi":"10.1080/15476286.2023.2290769","DOIUrl":"10.1080/15476286.2023.2290769","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD), which affects approximately 25% of the global population, is an urgent health issue leading to various metabolic comorbidities. Circular RNAs (circRNAs), covalently closed RNA molecules, are characterized by ubiquity, diversity, stability, and conservatism. Indeed, they participate in various biological processes via distinct mechanisms that could modify the natural history of NAFLD. In this review, we briefly introduce the biogenesis, characteristics, and biological functions of circRNAs. Furthermore, we summarize circRNAs expression profiles in NAFLD by intersecting seven sequencing data sets and describe the cellular roles of circRNAs and their potential advantages as biomarkers of NAFLD. In addition, we emphatically discuss the exosomal non-coding RNA sorting mechanisms and possible functions in recipient cells. Finally, we extensively discuss the potential application of targeting disease-related circRNAs and competing endogenous RNA networks through gain-of-function and loss-of-function approaches in targeted therapy of NAFLD.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138809125","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
Structure and function of the pseudouridine 5'-monophosphate glycosylase PUMY from Arabidopsis thaliana. 拟南芥中假尿苷-5'-单磷酸糖基化酶 PUMY 的结构和功能。
IF 4.1 3区 生物学
RNA Biology Pub Date : 2024-01-01 Epub Date: 2023-12-20 DOI: 10.1080/15476286.2023.2293340
Jeongyun Lee, Sang-Hoon Kim, Sangkee Rhee
{"title":"Structure and function of the pseudouridine 5'-monophosphate glycosylase PUMY from <i>Arabidopsis thaliana</i>.","authors":"Jeongyun Lee, Sang-Hoon Kim, Sangkee Rhee","doi":"10.1080/15476286.2023.2293340","DOIUrl":"10.1080/15476286.2023.2293340","url":null,"abstract":"<p><p>Pseudouridine is a noncanonical <i>C</i>-nucleoside containing a C-C glycosidic linkage between uracil and ribose. In the two-step degradation of pseudouridine, pseudouridine 5'-monophosphate glycosylase (PUMY) is responsible for the second step and catalyses the cleavage of the C-C glycosidic bond in pseudouridine 5'-monophosphate (ΨMP) into uridine and ribose 5'-phosphate, which are recycled via other metabolic pathways. Structural features of <i>Escherichia coli</i> PUMY have been reported, but the details of the substrate specificity of ΨMP were unknown. Here, we present three crystal structures of <i>Arabidopsis thaliana</i> PUMY in different ligation states and a kinetic analysis of ΨMP degradation. The results indicate that Thr149 and Asn308, which are conserved in the PUMY family, are structural determinants for recognizing the nucleobase of ΨMP. The distinct binding modes of ΨMP and ribose 5'-phosphate also suggest that the nucleobase, rather than the phosphate group, of ΨMP dictates the substrate-binding mode. An open-to-close transition of the active site is essential for catalysis, which is mediated by two α-helices, α11 and α12, near the active site. Mutational analysis validates the proposed roles of the active site residues in catalysis. Our structural and functional analyses provide further insight into the enzymatic features of PUMY towards ΨMP.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138809128","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
Epitranscriptomic regulation in fasting hearts: implications for cardiac health. 空腹心脏的表转录组调控:对心脏健康的影响。
IF 4.1 3区 生物学
RNA Biology Pub Date : 2024-01-01 Epub Date: 2024-02-07 DOI: 10.1080/15476286.2024.2307732
Daniel Benak, Kristyna Holzerova, Jaroslav Hrdlicka, Frantisek Kolar, Mark Olsen, Mati Karelson, Marketa Hlavackova
{"title":"Epitranscriptomic regulation in fasting hearts: implications for cardiac health.","authors":"Daniel Benak, Kristyna Holzerova, Jaroslav Hrdlicka, Frantisek Kolar, Mark Olsen, Mati Karelson, Marketa Hlavackova","doi":"10.1080/15476286.2024.2307732","DOIUrl":"10.1080/15476286.2024.2307732","url":null,"abstract":"<p><p>Cardiac tolerance to ischaemia can be increased by dietary interventions such as fasting, which is associated with significant changes in myocardial gene expression. Among the possible mechanisms of how gene expression may be altered are epigenetic modifications of RNA - epitranscriptomics. N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) and N<sup>6</sup>,2'-O-dimethyladenosine (m<sup>6</sup>Am) are two of the most prevalent modifications in mRNA. These methylations are reversible and regulated by proteins called writers, erasers, readers, and m<sup>6</sup>A-repelled proteins. We analysed 33 of these epitranscriptomic regulators in rat hearts after cardioprotective 3-day fasting using RT-qPCR, Western blot, and targeted proteomic analysis. We found that the most of these regulators were changed on mRNA or protein levels in fasting hearts, including up-regulation of both demethylases - FTO and ALKBH5. In accordance, decreased methylation (m<sup>6</sup>A+m<sup>6</sup>Am) levels were detected in cardiac total RNA after fasting. We also identified altered methylation levels in <i>Nox4</i> and <i>Hdac1</i> transcripts, both of which play a role in the cytoprotective action of ketone bodies produced during fasting. Furthermore, we investigated the impact of inhibiting demethylases ALKBH5 and FTO in adult rat primary cardiomyocytes (AVCMs). Our findings indicate that inhibiting these demethylases reduced the hypoxic tolerance of AVCMs isolated from fasting rats. This study showed that the complex epitranscriptomic machinery around m<sup>6</sup>A and m<sup>6</sup>Am modifications is regulated in the fasting hearts and might play an important role in cardiac adaptation to fasting, a well-known cardioprotective intervention.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703225","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
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