Journal Article

The CDK5 repressor CDK5RAP1 is a methylthiotransferase acting on nuclear and mitochondrial RNA

Veronika Reiter, Dorothea M.S. Matschkal, Mirko Wagner, Daniel Globisch, Andrea C. Kneuttinger, Markus Müller and Thomas Carell

in Nucleic Acids Research

Volume 40, issue 13, pages 6235-6240
Published in print July 2012 | ISSN: 0305-1048
Published online March 2012 | e-ISSN: 1362-4962 | DOI: http://dx.doi.org/10.1093/nar/gks240

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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 (i6A) into 2-methylthio-N6-isopentenyladenosine (ms2i6A). 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.

Journal Article.  3421 words.  Illustrated.

Subjects: Chemistry ; Biochemistry ; Bioinformatics and Computational Biology ; Genetics and Genomics ; Molecular and Cell Biology

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