22 Translational Control of TOP mRNAs

Abstract

Fundamental biological processes like cell proliferation, differentiation, development, and malignant transformation in eukaryotes involve changing requirements for the translational machinery. Observations made in recent years have disclosed that synthesis of many components of the translational apparatus is regulated at the translational level (Table 1). These include ribosomal proteins (rps) (Meyuhas et al. 1996); elongation factors 1A and 2; poly(A)-binding protein (PABP), which has been implicated in both translation initiation and ribosome assembly (see Sachs Chapter 10); P40, a protein that was isolated from rat 40S ribosomal subunit (Tohgo et al. 1994), whose yeast counterpart has been implicated in processing of the 20S rRNA precursor and maturation of the 40S ribosomal subunit (Ford et al. 1999); B23, a major phosphoprotein in the interphasic nucleolus (Zatsepina et al. 1999), which is a putative ribosome assembly factor; hnRNP A1, a protein that functions in nuclear splicing and export of mRNAs (Dreyfuss et al. 1993; Izaurralde et al. 1997); as well as a P23 that has been shown to be associated with microtubules, but whose function has not yet been identified (Gachet et al. 1999). It seems that resources and energy are wasted by resting cells for maintaining a large excess of inefficiently translated mRNAs, but this actually enables them to respond rapidly to mitogenic stimulations by having immediately available a large protein synthesis capacity.

A structural hallmark common to all the mRNAs above is the presence of a 5′ terminal oligopyrimidine tract (5′TOP), and therefore they are termed TOP mRNAs (Table 1). This...