Vertebrate mRNAs with a 5′-Terminal Pyrimidine Tract Are Candidates for Translational Repression in Quiescent Cells: Characterization of the Translational cis-Regulatory Element

Abstract

The translation of mammalian ribosomal protein (rp) mRNAs is selectively repressed in nongrowing cells. This response is mediated through a regulatory element residing in the 5′ untranslated region of these mRNAs and includes a 5′ terminal oligopyrimidine tract (5′ TOP). To further characterize the translational cis-regulatory element, we monitored the translational behavior of various endogenous and heterologous mRNAs or hybrid transcripts derived from transfected chimeric genes. The translational efficiency of these mRNAs was assessed in cells that either were growing normally or were growth arrested under various physiological conditions. Our experiments have yielded the following results: (i) the translation of mammalian rp mRNAs is properly regulated in amphibian cells, and likewise, amphibian rp mRNA is regulated in mammalian cells, indicating that all of the elements required for translation control of rp mRNAs are conserved among vertebrate classes; (ii) selective translational control is not confined to rp mRNAs, as mRNAs encoding the naturally occurring ubiquitin-rp fusion protein and elongation factor la, which contain a 5′ TOP, also conform this mode of regulation; (iii) rat rpP2 mRNA contains only five pyrimidines in its 5′ TOP, yet this mRNA is translationally controlled in the same fashion as other rp mRNAs with a 5′ TOP of eight or more pyrimidines; (iv) full manifestation of this mode of regulation seems to require both the 5′ TOP and sequences immediately downstream; and (v) an intact translational regulatory element from rpL32 mRNA fails to exert its regulatory properties even when preceded by a single A residue.