Protein-directed ribosomal frameshifting temporally regulates gene expression.

Napthine, Sawsan; Ling, Roger; Finch, Leanne K; Jones, Joshua D; Bell, Susanne; Brierley, Ian; Firth, Andrew E · Nat Commun · 2017

basic_science · Level V

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Abstract

Programmed -1 ribosomal frameshifting is a mechanism of gene expression, whereby specific signals within messenger RNAs direct a proportion of translating ribosomes to shift -1 nt and continue translating in the new reading frame. Such frameshifting normally occurs at a set ratio and is utilized in the expression of many viral genes and a number of cellular genes. An open question is whether proteins might function as trans-acting switches to turn frameshifting on or off in response to cellular conditions. Here we show that frameshifting in a model RNA virus, encephalomyocarditis virus, is trans-activated by viral protein 2A. As a result, the frameshifting efficiency increases from 0 to 70% (one of the highest known in a mammalian system) over the course of infection, temporally regulating the expression levels of the viral structural and enzymatic proteins.

Medical subject headings