FASTKD5 processes mitochondrial pre-mRNAs at noncanonical cleavage sites.

ABSTRACT: The first post-transcriptional step in mammalian mitochondrial gene expression, required for the synthesis of the 13 polypeptides encoded in mitochondrial DNA (mtDNA), is endonucleolytic cleavage of the primary polycistronic transcripts. Excision of the mtDNA-encoded transfer RNAs (tRNAs) releases most mature RNAs; however, processing of three noncanonical messenger RNAs (mRNAs) not flanked by tRNAs (CO1, CO3, and CYB) requires FASTKD5. To investigate the molecular mechanism involved, we created knockout human cell lines to use as assay systems. The absence of FASTKD5 produced a severe OXPHOS assembly defect due to the inability to translate two unprocessed noncanonical mRNAs and predicted altered folding patterns specifically at the 5'-end of the CO1 coding sequence. Structural features 1

SUBMITTER: Antonicka H 

PROVIDER: S-EPMC12242768 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature