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.The translation of vertebrate ribosomal protein (rp) mRNAs is largely regulated in a growth-dependent manner, as illustrated by their selective release from polysomes in growtharrested cells. This has been demonstrated during transition of various cells types between growing and nongrowing states in response to a wide variety of physiological stimuli, including dexamethasone-treated mouse lymphosarcoma cells (45,48), serum starvation of mouse fibroblasts (24,38) or Xenopus kidney cells (41), and differentiation of mouse myoblasts (1) and concanavalin A-treated bovine T cells (37). Similar specific translational fluctuations have been observed for rp mRNAs during the transition from the rapidly growing state in the fetal liver to the quiescent state in the adult and upon resumption of the hepatocyte proliferation in the regenerating liver (2). The mammalian, avian, and amphibian rp mRNAs that have been rigorously analyzed thus far contain a 5'-terminal oligopyrimidine tract (5' TOP), which consists of a C residue at the cap site, followed by an uninterrupted sequence of up to 13 pyrimidines (3,18,54,69,71). In attempt to delimit the translational regulatory element (TLRE), it has been shown that the 35-nucleotide-long 5' untranslated region (UTR) of Xenopus rpS19 is sufficient to confer translational repression on a chimeric mRNA in a developmental stage-dependent manner (43). The involv...

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