"Structure-function analysis of human TYW2 enzyme required for the biosynthesis of a highly modified Wybutosine (yW) base in phenylalanine-tRNA."

Rodriguez V, Vasudevan S, Noma A, Carlson BA, Green JE, Suzuki T, Chandrasekharappa SC



Published 2012-01-01 in PLoS One volume 7 .

Pubmed ID: 22761755
DOI identifier: -

Abstract:
Posttranscriptional modifications are critical for structure and function of tRNAs. Wybutosine (yW) and its derivatives are hyper-modified guanosines found at the position 37 of eukaryotic and archaeal tRNA(Phe). TYW2 is an enzyme that catalyzes alpha-amino-alpha-carboxypropyl transfer activity at the third step of yW biogenesis. Using complementation of a DeltaTYW2 strain, we demonstrate here that human TYW2 (hTYW2) is active in yeast and can synthesize the yW of yeast tRNA(Phe). Structure-guided analysis identified several conserved residues in hTYW2 that interact with S-adenosyl-methionine (AdoMet), and mutation studies revealed that K225 and E265 are critical residues for the enzymatic activity. We previously reported that the human TYW2 is overexpressed in breast cancer. However, no difference in the tRNA(Phe) modification status was observed in either normal mouse tissue or a mouse tumor model that overexpresses Tyw2, indicating that hTYW2 may have a role in tumorigenesis unrelated to yW biogenesis.


This publication refers to following proteins:



Last modification of this entry: Oct. 8, 2013