RT info:eu-repo/semantics/article
T1 Role of FAST kinase domains 3 (FASTKD3) in post-transcriptional regulation of mitochondrial gene expression
A1 Boehm, Erik
A1 Zornoza, María
A1 Jourdain, Alexis A.
A1 Delmiro Magdalena, Aitor
A1 García Consuegra, Inés
A1 Torres Merino, Rebeca
A1 Orduña Domingo, Antonio
A1 Martín Ferrero, Miguel Ángel
A1 Martinou, Jean-Claude
A1 Fuente García, Miguel Ángel de la
A1 Simarro Grande, María
K1 Gene expression
K1 Expresión génica
K1 Mitochondria
K1 Mitocondrias
K1 Post-transcriptional regulation
K1 Regulación postranscripcional
AB The Fas-activated serine/threonine kinase (FASTK) family of proteins has recently emerged as a central regulator of mitochondrial gene expression through the function of an unusual RNA-binding domain named RAP (for RNA-binding domain abundant in Apicomplexans), 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 knock-out 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.
PB American Society for Biochemistry and Molecular Biology
SN 1083-351X
YR 2016
FD 2016
LK http://uvadoc.uva.es/handle/10324/44626
UL http://uvadoc.uva.es/handle/10324/44626
LA eng
NO Journal of Biological Chemistry, 2016, vol. 291, n. 50. p. 25877-25887
NO Producción Científica
DS UVaDOC
RD 04-may-2024