Back to Search
Start Over
Role of FAST kinase domains 3 (FASTKD3) in post-transcriptional regulation of mitochondrial gene expression
- Source :
- UVaDOC: Repositorio Documental de la Universidad de Valladolid, Universidad de Valladolid, Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid, UVaDOC. Repositorio Documental de la Universidad de Valladolid, instname, Digital.CSIC. Repositorio Institucional del CSIC
- Publication Year :
- 2016
- Publisher :
- American Society for Biochemistry and Molecular Biology, 2016.
-
Abstract
- Producción Científica<br />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.<br />Junta de Castilla y León (grants BIO/ VA20/15 and BIO/VA21/15)<br />Swiss National Science Foundation (grant 310030B_160257/1)
- Subjects :
- 0301 basic medicine
translation control
Translation
RNA, Mitochondrial
RNA Stability
translation
Regulación postranscripcional
Biology
Protein Serine-Threonine Kinases
MT-RNR1
Biochemistry
Ribosome assembly
FASTKD5
Electron Transport Complex IV
Mitochondrial Proteins
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Gene expression
Translational regulation
Humans
RNA, Messenger
Molecular Biology
Post-transcriptional regulation
Mitocondrias
FASTKD3
RNA metabolism
Messenger RNA
RNA
Cell Biology
Protein-Serine-Threonine Kinases
Molecular biology
Cell biology
Mitochondria
030104 developmental biology
Gene Expression Regulation
Cyclooxygenase 1
030217 neurology & neurosurgery
Expresión génica
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- UVaDOC: Repositorio Documental de la Universidad de Valladolid, Universidad de Valladolid, Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid, UVaDOC. Repositorio Documental de la Universidad de Valladolid, instname, Digital.CSIC. Repositorio Institucional del CSIC
- Accession number :
- edsair.doi.dedup.....be368041998ed49aad615f24bcf70985