How the sequence of a gene can tune its translation

Abstract

Sixty-one codons specify 20 amino acids, offering cells many options for encoding a polypeptide sequence. Two new studies (Cannarrozzi et al., 2010; Tuller et al., 2010) now foster the idea that patterns of codon usage can control ribosome speed, fine-tuning translation to increase the efficiency of protein synthesis.

Figure 1. Messenger RNA sequences set the speed limit

There are three times as many codons as amino acids, meaning that a given amino acid can be encoded by several synonymous codons and identical proteins can be made from very different mRNA sequences. Codon choice is not random, but is highly selected across a broad range of organisms to optimize protein production. (A) For many genes, codons recognized by low-abundance tRNAs are overrepresented in the first part of the gene. This pattern suggests that ribosomes translate more slowly over the initial 50 codons or so (ramp stage), and then translate the remainder of the mRNA at full speed. The mRNA template itself controls the speed of ribosomes, somewhat analogous to how poor road conditions limit the speed of cars in a construction zone. (B) The arrangement of synonymous codons along a gene influences translation speed. Shown is a simple example in which two different codons (represented by different shades of blue) encode the same amino acid. When the identical codons are consecutively arranged along the mRNA (auto-correlated), translation is faster than when they are alternatively arranged (anti-correlated).