en
Scientific article
Open access
English

The FASTK family proteins fine-tune mitochondrial RNA processing

Published inPLOS genetics, vol. 17, no. 11, e1009873
Publication date2021-11-08
First online date2021-11-08
Abstract

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.

eng
Funding
Citation (ISO format)
OHKUBO, Akira et al. The FASTK family proteins fine-tune mitochondrial RNA processing. In: PLOS genetics, 2021, vol. 17, n° 11, p. e1009873. doi: 10.1371/journal.pgen.1009873
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal1553-7390
42views
3downloads

Technical informations

Creation01/16/2024 2:26:08 PM
First validation02/13/2024 2:00:26 PM
Update time02/13/2024 2:00:26 PM
Status update02/13/2024 2:00:26 PM
Last indexation05/06/2024 5:55:56 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack