2024-03-28T20:46:11Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1580972021-12-28T16:48:07Zcom_10261_39com_10261_1col_10261_292
Role of FAST kinase domains 3 (FASTKD3) in post-transcriptional regulation of mitochondrial gene expression
Boehm, Erik
Jourdain, Alexis A.
Torres-Merino, Rebeca
Orduña, Antonio
Martinou, Jean-Claude
Fuente, Miguel A. de la
Simarro-Grande, María
Swiss National Science Foundation
Roche
Junta de Castilla y León
Mitochondria
Translation
RNA metabolism
FASTKD3
The 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.
This work was supported by Consejería de Sanidad JCyL Grants BIO/VA20/15 (to M. S.) and BIO/VA21/15 (to M. A. D. l. F.), Roche Diagnostics S.L. (to M. S.), the Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Förschung Grant 310030B_160257/1 (to J. C. M.), iGE3, and the State of Geneva.
Peer Reviewed
2017-12-12T09:43:21Z
2017-12-12T09:43:21Z
2016
2017-12-12T09:43:21Z
artículo
http://purl.org/coar/resource_type/c_6501
doi: 10.1074/jbc.M116.730291
e-issn: 1083-351X
issn: 0021-9258
Journal of Biological Chemistry 291(50): 25877 (2016)
http://hdl.handle.net/10261/158097
10.1074/jbc.M116.730291
http://dx.doi.org/10.13039/100004337
http://dx.doi.org/10.13039/501100014180
27789713
Publisher's version
https://doi.org/10.1074/jbc.M116.730291
Sí
open
American Society for Biochemistry and Molecular Biology