ArticleNucleic acids research2025
FASTKD5 processes mitochondrial pre-mRNAs at noncanonical cleavage sites.
Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- Folding the message: mRNA structure as a regulatory layer of human mitochondrial gene expression.Biochimica et biophysica acta. Molecular cell research · 2026Review
- Mechanisms and disease relevance of mitochondrial translation in humans.Nature reviews. Molecular cell biology · 2026Review
- Human FASTK preferentially binds single-stranded and G-rich RNA.The FEBS journal · 2026Article
- FASTK post-transcriptional regulators - a 'FAST-tracK' in mitochondrial gene expression.Biochemical Society transactions · 2025Review
- Bi-allelic mutations in FASTKD5 are associated with cytochrome c oxidase deficiency and early- to late-onset Leigh syndrome.American journal of human genetics · 2025Article
- The mitochondrial methylation potential gates mitoribosome assembly.Nature communications · 2025Article
- The Vsr-like protein FASTKD4 regulates the stability and polyadenylation of the MT-ND3 mRNA.Nucleic acids research · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors.
Funding
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 13-15 nt upstream of the CO1 and CYB cleavage sites suggest FASTKD5 recognition mechanisms. Remarkably, a map of essential FASTKD5 amino acid residues revealed RNA substrate specificity; however, a key, putative active site residue was required for processing all three noncanonical pre-RNAs. Mutating this site did not significantly alter the binding of any client RNA substrate. A reconstituted in vitro system showed that wild-type, but not mutant, FASTKD5, was able to cleave client substrates correctly. These results establish FASTKD5 as the missing piece of biochemical machinery required to completely process the primary mitochondrial transcript.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.