Abstract

Author SummaryTranslation of mRNA into protein and turnover of mRNA are two points at which cells can exert regulatory control of gene expression, thereby ensuring that the protein products are present in cells and tissues at the appropriate time and place. The DDX6 family of DEAD box helicases, exemplified by the yeast protein Dhh1, is a group of well-conserved eukaryotic proteins that regulate translation and mRNA decay. As DDX6 proteins are known to be important for diverse processes such as cellular stress responses, early embryonic development, and replication of some viruses, understanding their mechanism of action could be of broad significance to many fields. Previous studies suggest that Dhh1 and other DDX6-family proteins mainly regulate translation at the initiation stage, triggering sequestration and/or decapping of the mRNA. Our work expands the potential functions of Dhh1, showing that Dhh1 is also capable of inhibiting translation at later stages when ribosomes are already loaded onto mRNAs. This extended function for Dhh1 allows a more robust translational control, as inhibition at a late stage of translation can provide immediate stoppage of protein production, as well as affording the potential for storing mRNA already primed and loaded with ribosomes for subsequent rapid re-utilization.

Highlights

  • Messenger RNA is targeted for destruction in a precise and regulated fashion

  • As DDX6 proteins are known to be important for diverse processes such as cellular stress responses, early embryonic development, and replication of some viruses, understanding their mechanism of action could be of broad significance to many fields

  • Previous studies suggest that Dhh1 and other DDX6-family proteins mainly regulate translation at the initiation stage, triggering sequestration and/or decapping of the Messenger RNA (mRNA)

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Summary

Introduction

Messenger RNA (mRNA) is targeted for destruction in a precise and regulated fashion. In eukaryotic cells, the digestion of the 39 polyadenosine tail (deadenylation) is the first step, followed predominantly by removal of the mRNA cap and 59R39 exonucleolytic digestion or, rarely, 39R59 degradation catalyzed by the cytoplasmic exosome [1]. MRNA decapping is catalyzed by a single polypeptide encoded by DCP2. DCP2 is conserved from yeast to humans, it is becoming apparent that additional decapping activities exist in metazoans [3]. The rate at which an mRNA 59 cap is removed is highly variable, and not completely understood, the rate of Dcp2-dependent mRNA decapping is modulated by a suite of protein factors that facilitate the binding and catalytic activity of the decapping enzyme itself. The exact nature of the relationship between mRNA translation and decay is unclear, it has been postulated that decapping activators may function to promote mRNA turnover by monitoring mRNA translational status and/or promoting translation states that favor the decapping reaction. Of the many factors that influence mRNA decapping rates, the function of the DEAD-box RNA helicase Dhh most clearly ties mRNA decapping to protein synthesis

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