Widespread non-modular overlapping codes in the coding regions*
Shaked Bergman, Tamir Tuller
Abstract
Messenger RNAs (mRNAs) consist of a coding region (open reading frame (ORF)) and two untranslated regions (UTRs), 5'UTR and 3'UTR. Ribosomes travel along the coding region, translating nucleotide triplets (called codons) to a chain of amino acids. The coding region was long believed to mainly encode the amino acid content of proteins, whereas regulatory signals reside in the UTRs and in other genomic regions. However, in recent years we have learned that the ORF is expansively populated with various regulatory signals, or codes, which are related to all gene expression steps and additional intracellular aspects. In this paper, we review the current knowledge related to overlapping codes inside the coding regions, such as the influence of synonymous codon usage on translation speed (and, in turn, the effect of translation speed on protein folding), ribosomal frameshifting, mRNA stability, methylation, splicing, transcription and more. All these codes come together and overlap in the ORF sequence, ensuring production of the right protein at the right time.