Frameshifting

Frameshifting is a translational recoding event in which the ribosome shifts its reading frame during protein synthesis, producing alternative polypeptides from a single mRNA. It can occur as a programmed regulatory mechanism or as a rare translational error, and it affects how much of each protein is produced from overlapping open reading frames.

A common form is the -1 frameshift. It is typically triggered by a slippery heptanucleotide sequence in the mRNA and a downstream stimulatory RNA structure, such as a pseudoknot or stem-loop. The ribosome pauses at the signal and the tRNA–mRNA contacts realign in the new frame, yielding a different coding sequence. Although -1 frameshifts are most studied, +1 frameshifts also occur in some systems.

Frameshifting is widespread in biology. It is well established in viral genomes, including retroviruses and coronaviruses, where it helps regulate essential protein ratios. It is also observed in bacteria and eukaryotes. By altering the reading frame, frameshifting can generate extended or fusion proteins, modulate enzyme activity, or fine-tune the production of multiple products from a single transcript.

Research and applications rely on various approaches, such as reporter gene assays and ribosome profiling, to quantify frameshift efficiency. In biotechnology, engineered frameshifts enable the co-expression of multiple proteins from one mRNA. In medicine, understanding frameshifting contributes to antiviral strategies aimed at disrupting viral protein synthesis.