The FASTK family proteins fine-tune mitochondrial RNA processing

Article Article scientifique Article The FASTK family proteins fine-tune mitochondrial RNA processing eng 2021-11-08 2021-11-08 author Ohkubo Akira 0000-0002-5441-8547 858721 author Van Haute Lindsey 0000-0001-7809-1473 author Rudler Danielle L. 0000-0002-5540-6548 author Stentenbach Maike 0000-0002-1933-9149 author Steiner Florian 0000-0002-0514-5060 829674 Département de biologie moléculaire et cellulaire (MOCEL) author Rackham Oliver 0000-0002-5301-9624 author Minczuk Michal 0000-0001-8242-1420 author Filipovska Aleksandra 0000-0002-6998-8403 author Martinou Jean-Claude 0000-0002-9847-2051 27293 Département de biologie moléculaire et cellulaire (MOCEL) e1009873 10.1371/journal.pgen.1009873 34748562 1553-7390 PMC8601606 https://dx.plos.org/10.1371/journal.pgen.1009873 <p> Transcription of the human mitochondrial genome and correct processing of the two long polycistronic transcripts are crucial for oxidative phosphorylation. According to the tRNA punctuation model, nucleolytic processing of these large precursor transcripts occurs mainly through the excision of the tRNAs that flank most rRNAs and mRNAs. However, some mRNAs are not punctuated by tRNAs, and it remains largely unknown how these non-canonical junctions are resolved. The FASTK family proteins are emerging as key players in non-canonical RNA processing. Here, we have generated human cell lines carrying single or combined knockouts of several FASTK family members to investigate their roles in non-canonical RNA processing. The most striking phenotypes were obtained with loss of FASTKD4 and FASTKD5 and with their combined double knockout. Comprehensive mitochondrial transcriptome analyses of these cell lines revealed a defect in processing at several canonical and non-canonical RNA junctions, accompanied by an increase in specific antisense transcripts. Loss of FASTKD5 led to the most severe phenotype with marked defects in mitochondrial translation of key components of the electron transport chain complexes and in oxidative phosphorylation. We reveal that the FASTK protein family members are crucial regulators of non-canonical junction and non-coding mitochondrial RNA processing. </p> Dewey 570 Australian Research Council (ARC) Discovery Projects - Grant ID: DP170103000 DP170103000 AU Discovery Projects UK Research and Innovation Mitochondrial Genetics MC_UU_00015/4 GB MRC UWA Postgraduate Scholarships The National Health and Medical Research Council APP1156747 The Cancer Council of Western Australia Swiss National Science Foundation Regulation of centromeric chromatin 175606 CH Projects 43 Département de biologie moléculaire 161 46 Département de biologie cellulaire 165 false PLOS genetics 17 11 c3dbcc88-ab42-4bb2-a607-2b3aa45dcfeb Article (Published version) Public Article-scientifique-from-unpaywall.pdf 3563273 application/pdf CC BY-4.0 a3b1332fcf5c718bcbafe73a7f037b6b6e368743247fd07b259218a79b767aa6 openAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire Faculté des sciences / Section de biologie / Département de biologie cellulaire

Title	Published in	Year	Views	Downloads

The FASTK family proteins fine-tune mitochondrial RNA processing	PLOS genetics	2021	135	79
The FASTK Protein Family: Exploring Non-canonical Mitochondrial RNA Processing		2020	601	101

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Ohkubo, Akira