Pseudoknots, RNA Folding, and Translational Regulation

Abstract

The primary function of messenger RNAs is to encode genetic information, but mRNAs also encode signals that modulate translational efficiency and regulate gene expression. These signals include sequences and structures that define processing sites in higher organisms, enhance the probability of frameshift events or stop codon readthrough, and serve as targets for translational repressors. The concern of this review is the phenomenon of specific protein-mRNA interactions that regulate translational initiation. The first example of a protein translational repressor was found in RNA phages, where the phage coat protein binds to the translational initiation site for the replicase gene and shuts down replicase synthesis late in phage infection (Nathans et al. 1969; Spahr et al. 1969). Subsequently, a number of examples of translational regulation were discovered in T4 phage, including autoregulation of gene 32 and gene 43 (DNA polymerase), and regulation of a number of genes by the regA gene product (Gold 1988). About the same time, it was realized that Escherichia coli makes extensive use of translational feedback regulation to match ribosomal protein synthesis to the rate of ribosomal RNA synthesis (Nomura et al. 1984). Other E. coli proteins are now known to regulate their own synthesis at the translational level also. Repression at the transcriptional level is frequently a simple matter of competition between RNA polymerase and a repressor protein for binding to overlapping sites, as recently demonstrated for the lac operon (Schlax et al. 1995). The DNA tends to be a passive participant in this process, providing only...