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Role of FAST kinase domains 3 (FASTKD3) in post-transcriptional regulation of mitochondrial gene expression

AutorBoehm, Erik; Jourdain, Alexis A.; Torres-Merino, Rebeca; Orduña, Antonio; Martinou, Jean-Claude; Fuente, Miguel A. de la; Simarro-Grande, María
Palabras claveMitochondria
RNA metabolism
Fecha de publicación2016
EditorAmerican Society for Biochemistry and Molecular Biology
CitaciónJournal of Biological Chemistry 291(50): 25877 (2016)
ResumenThe FASTK family of proteins has recently emerged as a central regulator of mitochondrial gene expression through the function of an unusual RNA-binding domains named RAP, shared by all six members of the family. Here we describe the role of one of the less characterized members, FASTKD3, in mitochondrial RNA metabolism. First, we show that, in contrast to FASTK, FASTKD2 and FASTKD5, FASTKD3 does not localize in mitochondrial RNA granules, which are sites of processing and maturation of mtRNAs and ribosome biogenesis. Second, we generated FASTKD3 homozygous knockout cell lines by homologous recombination and observed that the absence of FASTKD3 resulted in increased steady-state levels and half-lives of a subset of mature mitochondrial mRNAs: ND2, ND3, CYTB, COX2 and ATP8/6. No aberrant processing of RNA precursors was observed. Rescue experiments demonstrated that RAP domain is required for FASTKD3 function in mRNA stability. Besides, we describe that FASTKD3 is required for efficient COX1 mRNA translation without altering mRNA levels, which results in a decrease in the steady-state levels of COX1 protein. This finding is associated with reduced mitochondrial complex IV assembly and activity. Our observations suggest that the function of this family of proteins goes beyond RNA processing and ribosome assembly and includes RNA stability and translation regulation within mitochondria.
Versión del editorhttps://doi.org/10.1074/jbc.M116.730291
Identificadoresdoi: 10.1074/jbc.M116.730291
e-issn: 1083-351X
issn: 0021-9258
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