Correction: Conserved mRNA-granule component Scd6 targets Dhh1 to repress translation initiation and activates Dcp2-mediated mRNA decay in vivo.
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ABSTRACT:
SUBMITTER: Zeidan Q
PROVIDER: S-EPMC6650028 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
Correction: Conserved mRNA-granule component Scd6 targets Dhh1 to repress translation initiation and activates Dcp2-mediated mRNA decay in vivo.
Zeidan Quira Q He Feng F Zhang Fan F Zhang Hongen H Jacobson Allan A Hinnebusch Alan G AG
PLoS genetics 20190723 7
[This corrects the article DOI: 10.1371/journal.pgen.1007806.]. ...[more]
Similar Datasets
Project description:Scd6 protein family members are evolutionarily conserved components of translationally silent mRNA granules. Yeast Scd6 interacts with Dcp2 and Dhh1, respectively a subunit and a regulator of the mRNA decapping enzyme, and also associates with translation initiation factor eIF4G to inhibit translation in cell extracts. However, the role of Scd6 in mRNA turnover and translational repression in vivo is unclear. We demonstrate that tethering Scd6 to a GFP reporter mRNA reduces mRNA abundance via Dcp2 and suppresses reporter mRNA translation via Dhh1. Thus, in a dcp2? mutant, tethered Scd6 reduces GFP protein expression with little effect on mRNA abundance, whereas tethered Scd6 has no impact on GFP protein or mRNA expression in a dcp2? dhh1? double mutant. The conserved LSm domain of Scd6 is required for translational repression and mRNA turnover by tethered Scd6. Both functions are enhanced in a ccr4? mutant, suggesting that the deadenylase function of Ccr4-Not complex interferes with a more efficient repression pathway enlisted by Scd6. Ribosome profiling and RNA-Seq analysis of scd6? and dhh1? mutants suggests that Scd6 cooperates with Dhh1 in translational repression and turnover of particular native mRNAs, with both processes dependent on Dcp2. Our results suggest that Scd6 can (i) recruit Dhh1 to confer translational repression and (ii) activate mRNA decapping by Dcp2 with attendant degradation of specific mRNAs in vivo, in a manner dependent on the Scd6 LSm domain and modulated by Ccr4.
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Project description:Conserved mRNA-granule component Scd6 targets Dhh1 to repress translation initiation and activates Dcp2-mediated mRNA decay in vivo
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Project description:Degradation of many yeast mRNAs involves decapping by Dcp1:Dcp2. Previous studies on decapping activators Edc3 and Scd6 suggested limited roles in promoting mRNA decay in yeast cells. RNA-seq analysis of mutants lacking one or both proteins reveals that Scd6 and Edc3 have largely redundant activities in targeting numerous mRNAs for degradation, which are masked in the single mutants. These transcripts are frequently targeted by decapping activators Dhh1 and Pat1 and the evidence suggests that Scd6/Edc3 act interchangeably to recruit Dhh1 to Dcp2 independently of Pat1. Ribosome profiling shows that redundancy between Scd6 and Edc3 and their functional interactions with Dhh1 and Pat1 extends to translational repression of particular transcripts, including a cohort of poorly translated mRNAs displaying interdependent regulation by all four factors. Scd6/Edc3 also participate with Dhh1/Pat1 in post-transcriptional repression of proteins required for respiration and catabolism of non-optimal carbon sources, which are normally expressed only in limiting glucose. Simultaneously eliminating Scd6/Edc3 increases mitochondrial membrane potential and elevates metabolites of the tricarboxylic acid and glyoxylate cycles critical for growth at low glucose levels. Thus, Scd6/Edc3 act redundantly, in parallel with Dhh1 and in cooperation with Pat1, to adjust gene expression to nutrient availability by controlling mRNA decapping and decay.
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