Wl. Chou et Zf. Chang, Cap-independent translation conferred by the 5 '-untranslated region of human thymidine kinase mRNA, BBA-GENE ST, 1519(3), 2001, pp. 209-215
Citations number
28
Categorie Soggetti
Molecular Biology & Genetics
Journal title
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
Translational control is one of the mechanisms that regulate thymidine kina
se (TK) expression in the cell cycle. Evidence for the TK mRNA sequence tha
t is involved in its own translation has been lacking. In this report, we s
how that TK-deficient mouse fibroblasts transfected with pFLAG-TK express a
TK mRNA containing the 5 ' -untranslated region (5 ' UTR) and produce two
polypeptides, FLAG-TK and TK, resulting from an alternative initiation of t
ranslation. Most interestingly, the 5 ' UTR of TK allowed the translation o
f FLAG-TK mRNA to become cap-independent in an in vitro translation system.
Furthermore, this 5 ' UTR sequence decreased significantly the efficiency
of translation from the AUG codon of FLAG when the concentration of FLAG-TK
RNA was low. Here, we also show that in normal human IMR-90 fibroblasts th
e induction of TK polypeptide by serum stimulation is insensitive to rapamy
cin treatment, which is known to inhibit the translations of transcripts of
some growth-controlled genes by affecting the cap-binding efficiency. Take
n together, we propose that the 5 ' UTR in TK mRNA might actually confer a
secondary structure to regulate ribosome binding during translation in a ca
p-independent manner. (C) 2001 Published by Elsevier Science B.V.