REGULATION OF P56(LCK) MESSENGER TURNOVER UPON T-CELL ACTIVATION - INVOLVEMENT OF THE 3'-UNTRANSLATED REGION IN STABILITY AS DETERMINED IN CELL-FREE-EXTRACTS

Full activation of T lymphocytes transiently down-regulates the steady state level of the tyrosine kinase p58(lck) mRNA. Here, we show that a decrease in messenger stability is involved in this downmodulation f ollowed thereafter by a rapid and marked increase in mRNA half-life. I n order to facilitate the study of p56(lck) messenger stability, an in vitro mRNA decay assay was developed and used to determine whether th e 451 nucleotide long 3' untranslated region (3'UTR) of the messenger is implicated in the regulation of mRNA stability. Indeed, deletion of most of the 3'UTR led to a substantial increase in transcript half-li fe whereas deletion of a limited 3' portion did not, thus showing that the 146 nucleotides located in 5' of the 3'UTR contain destabilizing elements. Furthermore, the stability of both truncated transcripts was still modulated upon activation, thereby suggesting that the activati on-responsive elements are located in a region distinct from the 3'UTR . (C) 1997 Academic Press.