BioProject

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. More...

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. Overall design: Ribosome profile and RNA-sequencing studies include total 16 samples, 8 for ribosome profiling and 8 for total RNA-sequencing from duplicate cultures of WT, edc3∆, scd6∆, and edc3∆scd6∆ yeast strains. The RNA-Seq samples had ERCC Spike-In added to the samples. Yeast strains were grown in YPD to OD600 = 0.6~0.8 at 30˚C, then flash frozen. Ribosome protected or total RNA libraries were prepared from yeast cells and sequenced. Less...