ArticleNucleic acids research2017
FASTKD1 and FASTKD4 have opposite effects on expression of specific mitochondrial RNAs, depending upon their endonuclease-like RAP domain.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
- Targeting Tumour Microtubes to Disrupt Glioma Networks.Research square · 2026Article
- Searching for α-solenoid proteins involved in organellar gene expression.BMC genomics · 2026Article
- 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
- Transcription arrest induces formation of RNA granules in mitochondria.Life science alliance · 2025Article
- RAP proteins regulate apicoplast noncoding RNA processing in Plasmodium falciparum.Cell reports · 2025Article
- FASTKD5 processes mitochondrial pre-mRNAs at noncanonical cleavage sites.Nucleic acids research · 2025Article
- Article
- Engineered mitochondria in diseases: mechanisms, strategies, and applications.Signal transduction and targeted therapy · 2025Review
- The Vsr-like protein FASTKD4 regulates the stability and polyadenylation of the MT-ND3 mRNA.Nucleic acids research · 2025Article
- Unraveling the roles and mechanisms of mitochondrial translation in normal and malignant hematopoiesis.Journal of hematology & oncology · 2024Review
- FASTKD1 as a diagnostic and prognostic biomarker for STAD: Insights into m6A modification and immune infiltration.Experimental and therapeutic medicine · 2024Article
- The molecular machinery for maturation of primary mtDNA transcripts.Human molecular genetics · 2024Review
- Cardiac Myocyte-Specific Overexpression of FASTKD1 Prevents Ventricular Rupture After Myocardial Infarction.Journal of the American Heart Association · 2023Article
- Expression profiles of lncRNAs and their possible regulatory role in monocrotaline-induced HSOS in rats.Frontiers in genetics · 2023Article
- A novel homozygous missense mutation in the FASTKD2 gene leads to Lennox-Gastaut syndrome.Journal of human genetics · 2022Article
- ANGEL2 phosphatase activity is required for non-canonical mitochondrial RNA processing.Nature communications · 2022Article
- Identification of human mitochondrial RNA cleavage sites and candidate RNA processing factors.BMC biology · 2022Article
- How RNases Shape Mitochondrial Transcriptomes.International journal of molecular sciences · 2022Review
- Functional genomics of RAP proteins and their role in mitoribosome regulation in Plasmodium falciparum.Nature communications · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
FASTK family proteins have been identified as regulators of mitochondrial RNA homeostasis linked to mitochondrial diseases, but much remains unknown about these proteins. We show that CRISPR-mediated disruption of FASTKD1 increases ND3 mRNA level, while disruption of FASTKD4 reduces the level of ND3 and of other mature mRNAs including ND5 and CYB, and causes accumulation of ND5-CYB precursor RNA. Disrupting both FASTKD1 and FASTKD4 in the same cell results in decreased ND3 mRNA similar to the effect of depleting FASTKD4 alone, indicating that FASTKD4 loss is epistatic. Interestingly, very low levels of FASTKD4 are sufficient to prevent ND3 loss and ND5-CYB precursor accumulation, suggesting that FASTKD4 may act catalytically. Furthermore, structural modeling predicts that each RAP domain of FASTK proteins contains a nuclease fold with a conserved aspartate residue at the putative active site. Accordingly, mutation of this residue in FASTKD4 abolishes its function. Experiments with FASTK chimeras indicate that the RAP domain is essential for the function of the FASTK proteins, while the region upstream determines RNA targeting and protein localization. In conclusion, this paper identifies new aspects of FASTK protein biology and suggests that the RAP domain function depends on an intrinsic nucleolytic activity.
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