Mitogenic and Nutritional Signals Are Transduced into Translational Efficiency of TOP mRNAs

Excerpt

Modulation of the abundance of the translational apparatus appears to enable eukaryotic cells to cope withchanging requirements for protein synthesis during transitions between extreme growth and nutritional states.Thus, rRNA synthesis is down-regulated when cellscease to proliferate or are deprived of amino acids and isup-regulated upon reversal of such conditions (Grummt1999 and references therein). Likewise, the translationalefficiency of mRNAs encoding many protein components of the translational machinery is similarly regulated. These include ribosomal proteins (Meyuhas et al.1996a; Meyuhas and Hornstein 2000 and referencestherein); elongation factor 1A (Rao and Slobin 1987;Avni et al. 1994; Jefferies et al. 1994a) and elongationfactor 2 (Terada et al. 1994; Avni et al. 1997); poly(A)-binding protein (Hornstein et al. 1999), which has beenimplicated in both translation initiation and ribosome assembly (Sachs 2000); and a few other proteins that havebeen implicated in ribosome assembly or nuclear-cytoplasmic transport of RNA (for review, see Meyuhas2000). The corresponding mRNAs are characterized bythe presence of a 5′ terminal oligopyrimidine tract(5′TOP) and therefore are referred to as TOP mRNAs.This structural motif comprises the core of the translational cis-regulatory element of these mRNAs, and itsfeatures are summarized elsewhere (Meyuhas and Hornstein 2000)...