RRC ID 35484
Author Reiter V, Matschkal DM, Wagner M, Globisch D, Kneuttinger AC, Müller M, Carell T.
Title The CDK5 repressor CDK5RAP1 is a methylthiotransferase acting on nuclear and mitochondrial RNA.
Journal Nucleic Acids Res
Abstract The unusual cyclin-dependent protein kinase 5 (CDK5) was discovered based on its sequence homology to cell cycle regulating CDKs. CDK5 was found to be active in brain tissues, where it is not involved in cell cycle regulation but in the regulation of neuronal cell differentiation and neurocytoskeleton dynamics. An aberrant regulation of CDK5 leads to the development of various neurodegenerative diseases including Alzheimer's disease. Although CDK5 is not regulated by cyclins, its activity does depend on the association with a protein activator and the presence or absence of further inhibitory factors. Recently, CDK5RAP1 was discovered to inhibit the active CDK5 kinase. Here, we show that CDK5RAP1 is a radical SAM enzyme, which postsynthetically converts the RNA modification N6-isopentenyladenosine (i(6)A) into 2-methylthio-N6-isopentenyladenosine (ms(2)i(6)A). This conversion is surprisingly not limited to mitochondrial tRNA, where the modification was known to exist. Instead, CDK5RAP1 introduces the modification also into nuclear RNA species establishing a link between postsynthetic kinase-based protein modification and postsynthetic RNA modification.
Volume 40(13)
Pages 6235-40
Published 2012-7-1
DOI 10.1093/nar/gks240
PII gks240
PMID 22422838
PMC PMC3401430
MeSH Cell Nucleus / enzymology Cell Nucleus / genetics HeLa Cells Humans Intracellular Signaling Peptides and Proteins / analysis Intracellular Signaling Peptides and Proteins / metabolism* Isopentenyladenosine / analogs & derivatives* Isopentenyladenosine / analysis Isopentenyladenosine / metabolism Mitochondria / enzymology Nerve Tissue Proteins / analysis Nerve Tissue Proteins / metabolism* RNA / chemistry RNA / metabolism* RNA, Mitochondrial RNA, Transfer / chemistry RNA, Transfer / metabolism Sulfurtransferases / metabolism*
IF 11.502
Times Cited 33
Prokaryotes E. coli ME9062(BW25113) JW0658-KC