PMID- 22422838
OWN - NLM
STAT- MEDLINE
DCOM- 20121022
LR  - 20220314
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 40
IP  - 13
DP  - 2012 Jul
TI  - The CDK5 repressor CDK5RAP1 is a methylthiotransferase acting on nuclear and 
      mitochondrial RNA.
PG  - 6235-40
LID - 10.1093/nar/gks240 [doi]
AB  - 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.
FAU - Reiter, Veronika
AU  - Reiter V
AD  - Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, 
      Ludwig-Maximilians University, Munich 81377, Germany.
FAU - Matschkal, Dorothea M S
AU  - Matschkal DM
FAU - Wagner, Mirko
AU  - Wagner M
FAU - Globisch, Daniel
AU  - Globisch D
FAU - Kneuttinger, Andrea C
AU  - Kneuttinger AC
FAU - Muller, Markus
AU  - Muller M
FAU - Carell, Thomas
AU  - Carell T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120315
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Mitochondrial)
RN  - 20859-00-1 (2-methylthio-N-6-isopentenyladenosine)
RN  - 63231-63-0 (RNA)
RN  - 7724-76-7 (Isopentenyladenosine)
RN  - 9014-25-9 (RNA, Transfer)
RN  - EC 2.8.- (CDK5RAP1 protein, human)
RN  - EC 2.8.1.- (Sulfurtransferases)
SB  - IM
MH  - Cell Nucleus/enzymology/genetics
MH  - HeLa Cells
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/analysis/*metabolism
MH  - Isopentenyladenosine/*analogs & derivatives/analysis/metabolism
MH  - Mitochondria/enzymology
MH  - Nerve Tissue Proteins/analysis/*metabolism
MH  - RNA/chemistry/*metabolism
MH  - RNA, Mitochondrial
MH  - RNA, Transfer/chemistry/metabolism
MH  - Sulfurtransferases/*metabolism
PMC - PMC3401430
EDAT- 2012/03/17 06:00
MHDA- 2012/10/23 06:00
PMCR- 2012/03/15
CRDT- 2012/03/17 06:00
PHST- 2012/03/17 06:00 [entrez]
PHST- 2012/03/17 06:00 [pubmed]
PHST- 2012/10/23 06:00 [medline]
PHST- 2012/03/15 00:00 [pmc-release]
AID - gks240 [pii]
AID - 10.1093/nar/gks240 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2012 Jul;40(13):6235-40. doi: 10.1093/nar/gks240. Epub 2012 
      Mar 15.