FASTK family proteins regulate processing and stability of mitochondrial RNAs

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Homo sapiens
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Fas-activated serine/threonine kinase (FASTK) and its homologs FASTKD1-5 each contain three conserved domains (FAST_1, FAST_2, and RAP) that bind RNA (Castello et al. 2012, Baltz et al. 2012). FASTKD1-5 and the short isoform of FASTK localize to mitochondria where they participate in regulating the processing and stability of RNA (Simarro et al. 2010, reviewed in Jourdain et al. 2017).
FASTK interacts with the 3' end of the MT-ND6 mRNA and protects the mRNA from degradation by the degradosome, SUPV3L1:PNPT1 (Jourdain et al. 2015). The MT-ND6 mRNA is unusual in being processed from the large L-strand precursor without flanking tRNA genes and thus without canonical processing by RNAse P and RNase Z. FASTK may, therefore, participate in an uncharacterized non-canonical mechanism of RNA processing or protect 3' ends produced by such a mechanism.
FASTKD1 acts to reduce the abundance of the MT-ND3 mRNA by an uncharacterized mechanism (Boehm et al. 2017).
FASTKD2 binds the 16S rRNA and the MT-ND6 mRNA and participates in their processing and expression (Antonicka and Shoubridge 2015, Popow et al. 2015). FASTKD2 interacts with several mitochondrial proteins including MTERFD1, TRUB2, WBSCR16, and NGRN (Antonicka et al. 2017).
FASTKD3 increases levels of five mitochondrial mRNAs (MT-ND2, MT-ND3, MT-CYB, MT-CO2, and the MT-ATP8/6 bicistronic mRNA) and increases translation of MT-CO1 mRNA through uncharacterized mechanisms (Boehm et al. 2016, Ohkubo et al. 2021).
TBRG4 (FASTKD4) binds most RNAs transcribed from the H-strand and enhances the expression levels of MT-ATP8/6, MT-CO1, MT-CO2, MT-CO3, MT-ND3, MT-CYB, and MT-ND5 mRNAs (Wolf and Mootha 2014, Boehm et al. 2017, Ohkubo et al. 2021). TBRG4 stabilizes MT-CO1, MT-ND3, and MT-CO2 mRNAs and assists the processing of MT-ND5 and MT-CYB mRNAs (Boehm et al. 2017, Ohkubo et al. 2021).
FASTKD5 binds 12S rRNA and all mRNAs except MT-ND3 and reduces levels of MT-ATP8/6, MT-CO1, MT-CO3, MT-ND5, and MT-CYB mRNAs (Antonicka and Shoubridge 2015, Ohkubo et al. 2021). .
Literature References
PubMed ID Title Journal Year
24746820 Functional genomic analysis of human mitochondrial RNA processing

Wolf, AR, Mootha, VK

Cell Rep 2014
28335001 FASTKD1 and FASTKD4 have opposite effects on expression of specific mitochondrial RNAs, depending upon their endonuclease-like RAP domain

Zaganelli, S, Boehm, E, Maundrell, K, Thore, S, Martinou, JC, Jourdain, AA

Nucleic Acids Res 2017
27789713 Role of FAST Kinase Domains 3 (FASTKD3) in Post-transcriptional Regulation of Mitochondrial Gene Expression

Orduña, A, Boehm, E, Delmiro Magdalena, A, Zornoza, M, Simarro, M, Martín, MA, de la Fuente, MA, Martinou, JC, Torres Merino, R, García-Consuegra, I, Jourdain, AA

J Biol Chem 2016
22658674 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins

Humphreys, DT, Strein, C, Preiss, T, Castello, A, Eichelbaum, K, Beckmann, BM, Horos, R, Krijgsveld, J, Fischer, B, Hentze, MW, Davey, NE, Steinmetz, LM

Cell 2012
22681889 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts

Landthaler, M, Murakawa, Y, Selbach, M, Wyler, E, Milek, M, Penfold-Brown, D, Schueler, M, Munschauer, M, Dieterich, C, Youngs, N, Schwanhäusser, B, Bonneau, R, Drew, K, Vasile, A, Baltz, AG

Mol Cell 2012
29036396 The FASTK family of proteins: emerging regulators of mitochondrial RNA biology

Anderson, P, Simarro, M, de la Fuente, MA, Martinou, JC, Popow, J, Jourdain, AA

Nucleic Acids Res 2017
26370583 FASTKD2 is an RNA-binding protein required for mitochondrial RNA processing and translation

Sauer, S, Curk, T, Schwarzl, T, Alleaume, AM, Hentze, MW, Popow, J

RNA 2015
25704814 A mitochondria-specific isoform of FASTK is present in mitochondrial RNA granules and regulates gene expression and function

Enriquez, JA, Anderson, P, Guaras, AM, Maundrell, K, Simarro, M, Rodley, CD, Reynier, P, Martinou, JC, Gueguen, N, Koppen, M, Jourdain, AA

Cell Rep 2015
34748562 The FASTK family proteins fine-tune mitochondrial RNA processing

Minczuk, M, Stentenbach, M, Filipovska, A, Van Haute, L, Martinou, JC, Rudler, DL, Steiner, FA, Rackham, O, Ohkubo, A

PLoS Genet 2021
27974379 A pseudouridine synthase module is essential for mitochondrial protein synthesis and cell viability

Antonicka, H, Choquet, K, Lin, ZY, Kleinman, CL, Shoubridge, EA, Gingras, AC

EMBO Rep 2017
25683715 Mitochondrial RNA Granules Are Centers for Posttranscriptional RNA Processing and Ribosome Biogenesis

Antonicka, H, Shoubridge, EA

Cell Rep 2015
20869947 Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration

Anderson, P, Benarafa, C, Marto, JA, Simarro, M, Tisdale, S, Orduña, A, Kedersha, N, Danial, N, Adelmant, GO, Gimenez-Cassina, A, Rhee, K, Lazaro, JB

Biochem Biophys Res Commun 2010
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