Widespread non-modular overlapping codes in the coding regions

Shaked Bergman, Tamir Tuller*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Article number031002
JournalPhysical Biology
Issue number3
StatePublished - May 2020


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