Louise Lambert, Amandine Moretton, Géraldine Farge
{"title":"Post-Transcriptional Modifications and Regulation of mRNAs in Human Mitochondria.","authors":"Louise Lambert, Amandine Moretton, Géraldine Farge","doi":"10.1016/j.biochi.2025.06.015","DOIUrl":null,"url":null,"abstract":"<p><p>Mitochondria contain their own circular genome (mtDNA), which encodes essential components of the oxidative phosphorylation (OXPHOS) system. Mitochondrial DNA transcription is a unique and relatively simple process, requiring a specialized transcription machinery that consists of a RNA polymerase (POLRMT), two transcription factors (TFAM and TFB2M), and an elongation factor (TEFM). During transcription, a non-canonical initiating nucleotide (NCIN) can be incorporated as the first nucleotide, serving as a 5' cap. Mitochondrial transcription produces large polycistronic transcripts, which are subsequently processed by ribonucleases to generate individual messenger RNAs (mt-mRNAs), ribosomal RNAs (mt-rRNAs), and transfer RNAs (mt-tRNAs). This review will specifically focus on the maturation and regulation of mt-mRNAs. Following their release from the primary transcript, mt-mRNAs undergo various post-transcriptional modifications, including methylation, pseudouridylation, and polyadenylation. These modifications play a crucial role in determining mt-mRNAs fate by influencing their stability, translation efficiency, and overall mitochondrial function. Additionally, the spatial organization of these processes within mitochondrial RNA granules (MRGs) suggests a compartmentalized system for mitochondrial gene regulation, ensuring precise coordination between transcription, processing, and translation. A deeper understanding of these post-transcriptional modifications provides valuable insights into mitochondrial gene expression and its broader impact on cellular metabolism.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimie","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.biochi.2025.06.015","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Mitochondria contain their own circular genome (mtDNA), which encodes essential components of the oxidative phosphorylation (OXPHOS) system. Mitochondrial DNA transcription is a unique and relatively simple process, requiring a specialized transcription machinery that consists of a RNA polymerase (POLRMT), two transcription factors (TFAM and TFB2M), and an elongation factor (TEFM). During transcription, a non-canonical initiating nucleotide (NCIN) can be incorporated as the first nucleotide, serving as a 5' cap. Mitochondrial transcription produces large polycistronic transcripts, which are subsequently processed by ribonucleases to generate individual messenger RNAs (mt-mRNAs), ribosomal RNAs (mt-rRNAs), and transfer RNAs (mt-tRNAs). This review will specifically focus on the maturation and regulation of mt-mRNAs. Following their release from the primary transcript, mt-mRNAs undergo various post-transcriptional modifications, including methylation, pseudouridylation, and polyadenylation. These modifications play a crucial role in determining mt-mRNAs fate by influencing their stability, translation efficiency, and overall mitochondrial function. Additionally, the spatial organization of these processes within mitochondrial RNA granules (MRGs) suggests a compartmentalized system for mitochondrial gene regulation, ensuring precise coordination between transcription, processing, and translation. A deeper understanding of these post-transcriptional modifications provides valuable insights into mitochondrial gene expression and its broader impact on cellular metabolism.