蛋白质指导的核糖体移码在时间上调节基因表达。

Protein-directed ribosomal frameshifting temporally regulates gene expression.

机构信息

Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.

出版信息

Nat Commun. 2017 Jun 8;8:15582. doi: 10.1038/ncomms15582.

DOI:10.1038/ncomms15582

PMID:28593994

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5472766/

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.

摘要

-1 核糖体移码是一种基因表达的机制，在此机制中，信使 RNA 中的特定信号指导一部分正在翻译的核糖体移码 1nt，并在新的阅读框中继续翻译。这种移码通常以固定的比例发生，在许多病毒基因和一些细胞基因的表达中都被利用。一个悬而未决的问题是，蛋白质是否可以作为反式作用开关，根据细胞条件打开或关闭移码。在这里，我们表明，模型 RNA 病毒——脑心肌炎病毒中的移码是被病毒蛋白 2A 反式激活的。结果，移码效率从感染开始时的 0%增加到 70%（在哺乳动物系统中是已知的最高之一），从而在时间上调节了病毒结构和酶蛋白的表达水平。