Growth-dependent translational control of top mRNAS

O. Meyuhas*, D. Avni, Y. Bibermant, S. Shama, B. Ostareck, A. Ostareck-Lederer, M. W. Hentze

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

TOP mRNAs are vertebrate mRNAs containing a 5' terminal oligopyrimidine tract (5'TOP) and are candidates for growth-dependent translational control mediated through this motif. Both mammalian and plant cell-free translation systems (CFTSs), which derived from nongrowing cells, discriminate against a reporter mRNA (SI6-GH) initiating with the 5'TOP-of ribosomal protein (rp) S16 mRNA. C to A substitution at the cap site of S16-Gti mRNA, which abolishes tile translational control of the respective mRNA (CM3-GH) in cells, also renders it refractory to discrimination in vitro. Preincubation of both CFTSs with a short RNA oligonucleotide containing the first 16 nt of rpS16 mRNA in molar excess, completely relieves the translational repression of S16-GH mRNA, with no effect on CM3-GtI mRNA. Mutations within the pyrimidine tract eliminate the ability of this oligonucleotide to relieve the translational repression. These results suggest that the translational repression of TOP mRNAs in growth arrested cells is mediated through a titratable repressor. We have recently identified, in co-transfection experiments, a protein which is able to repress in vivo the translation of S16-GH mRNA. This repression is highly selective, as the protein fails to repress the translation of CM3-GH mRNA. Moreover, this protein exerts its translational repression only in resting cells. When this protein is added to wheat germ extract it represses the translation of S16-GH mRNA, but not that of the CM3-Gtt mRNA. Hence, this protein appears as a prime candidate to be the translational repressor of at lea.st some of the TOP mRNAs.

Original languageEnglish
Pages (from-to)A1283
JournalFASEB Journal
Volume11
Issue number9
StatePublished - 1997
Externally publishedYes

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