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START: STructure-Assisted RNA Translation.

Gilbert Eriani1, Franck Martin1

  • 1a Architecture et Réactivité de l'ARN UPR 9002, CNRS , Université de Strasbourg , Strasbourg , France.

RNA Biology
|September 4, 2018
PubMed
Summary

The yeast Ded1 helicase normally melts RNA structures for cap-dependent translation. When Ded1 is non-functional, RNA structures promote translation at alternative sites, down-regulating the main gene. This novel mechanism is named START.

Keywords:
Ded1/DDX3RNA helicaseTranslation initiationmessenger RNAribosomescanning

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Area of Science:

  • Molecular Biology
  • RNA Biology
  • Gene Regulation

Background:

  • Cap-dependent translation initiation is crucial for gene expression, involving ribosomal complex assembly and scanning of the 5' Untranslated Region (5'UTR).
  • RNA helicases, such as yeast Ded1 (mammalian DDX3 orthologue), are essential for resolving RNA secondary structures during translation initiation.
  • Dysfunctional helicases can lead to alternative translation events and altered gene expression.

Purpose of the Study:

  • To investigate the role of RNA secondary structures in translation initiation when the Ded1 helicase is non-functional.
  • To characterize a novel mechanism of translation regulation mediated by RNA structures.

Main Methods:

  • The study likely involved experiments analyzing translation initiation in yeast models with non-functional Ded1.
  • Methods may include RNA structure probing, ribosome profiling, and analysis of protein expression from main and upstream ORFs (uORFs).

Main Results:

  • Non-functional Ded1 leads to the utilization of Alternative Translation Initiation Sites (ATIS) within the 5'UTR.
  • RNA secondary structures downstream of ATIS were identified as key drivers of this alternative initiation.
  • This process results in the translation of uORFs and subsequent down-regulation of the main Open Reading Frame (ORF).

Conclusions:

  • A novel mechanism, termed STructure-Assisted-RNA-Translation (START), is proposed.
  • START describes how RNA secondary structures can directly promote translation initiation at alternative sites in the absence of helicase activity.
  • This mechanism provides a new layer of gene expression regulation, particularly under conditions of impaired translation initiation machinery.