A code within a code: how codons influence mRNA stability

Abstract

The genetic code was deciphered more than 50 years ago, but we are only now becoming aware of a second, hidden code. It is the concept of “codon optimality” that enters the scene of developmental and homeostatic gene expression, linking translation rates, mRNA stability, and tRNA abundance. Both at the biological and methodological levels, work by Giraldez and colleagues in this issue of The EMBO Journal paves the way for further analyses of such key regulatory mechanisms.

Figure 1. Codon optimality and its correlates

(A) A second genetic code, based on codon optimality, determines mRNA fate in maternal‐to‐zygotic transition in different organisms, as well as gene expression during homeostasis across human tissues. Codon optimality correlates with gene expression levels, tRNA levels, mRNA half‐life, translation efficiency, and poly(A) tail length. (B) Hypothesis: A potential regulatory event relies on the translating polypeptide recognizing its own mRNA according to the preponderance of non‐optimal codons, and leading to the destabilization of the mRNA, probably associated with a slower translation rate and lower overall translation efficiency. In yellow, the growing polypeptide chain; in dark blue, translation efficiency (full line, high; dashed line, low). AG rich are optimal codons; CU rich are non‐optimal codons.