Whisper mutations: cryptic messages within the genetic code

• Published in: Oncogene Vol. 35; no. 29; pp. 3753 - 3759
• Main Authors: Fåhraeus, R, Marin, M, Olivares-Illana, V
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.07.2016; Nature Publishing Group
• Subjects: 631/80; Apoptosis; Cell Biology; Codon - genetics; Disease susceptibility; Gene expression; Gene mutations; Genetic aspects; Genetic code; Genetic Code - genetics; Genetics; Genomes; Health aspects; Human Genetics; Humans; Internal Medicine; Medicine; Medicine & Public Health; Models, Genetic; mRNA stability; Mutation; Oncology; Open reading frames; Open Reading Frames - genetics; Properties; Protein Biosynthesis - genetics; Protein Folding; Proteins; Proteins - chemistry; Proteins - genetics; Proteins - metabolism; review; RNA Folding; RNA Stability - genetics; RNA, Messenger - chemistry; RNA, Messenger - genetics
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2015.454

Recent years have seen a great expansion in our understandings of how silent mutations can drive a disease and that mRNAs are not only mere messengers between the genome and the encoded proteins but also encompass regulatory activities. This review focuses on how silent mutations within open reading frames can affect the functional properties of the encoded protein. We describe how mRNAs exert control of cell biological processes governed by the encoded proteins via translation kinetics, protein folding, mRNA stability, spatio-temporal protein expression and by direct interactions with cellular factors. These examples illustrate how additional levels of information lie within the coding sequences and that the degenerative genetic code is not redundant and have co-evolved with the encoded proteins. Hence, so called synonymous mutations are not always silent but ‘whisper’.