Abstract
ABSTRACTThe rate and regulation of mRNA decay are major elements in the proper control of gene expression. Edc3 and Lsm4 are two decapping activator proteins that have previously been shown to function in the assembly of RNA granules termed P bodies. Here, we show that deletion of edc3, when combined with a removal of the glutamine/asparagine rich region of Lsm4 (edc3Δ lsm4ΔC) reduces mRNA stability and alters pathways of mRNA degradation. Multiple tested mRNAs exhibited reduced stability in the edc3Δ lsm4ΔC mutant. The destabilization was linked to an increased dependence on Ccr4-mediated deadenylation and mRNA decapping. Unlike characterized mutations in decapping factors that either are neutral or are able to stabilize mRNA, the combined edc3Δ lsm4ΔC mutant reduced mRNA stability. We characterized the growth and activity of the major mRNA decay systems and translation in double mutant and wild-type yeast. In the edc3Δ lsm4ΔC mutant, we observed alterations in the levels of specific mRNA decay factors as well as nuclear accumulation of the catalytic subunit of the decapping enzyme Dcp2. Hence, we suggest that the effects on mRNA stability in the edc3Δ lsm4ΔC mutant may originate from mRNA decay protein abundance or changes in mRNPs, or alternatively may imply a role for P bodies in mRNA stabilization.
Highlights
The degradation of mRNAs is a fundamental process in the control and modulation of gene expression (Pérez-Ortín et al, 2012)
RESULTS mRNAs are destabilized by a synergistic effect of deletion of both EDC3 and the glutamine/asparagine rich domain of Lsm4 The edc3Δ lsm4ΔC mutant has been reported to be defective in the formation of P bodies (Decker et al, 2007)
When the two mutations were combined in the edc3Δ lsm4ΔC mutant, we found that the mutant exhibits reduced mRNA stability for mRNAs (Fig. 2C)
Summary
The degradation of mRNAs is a fundamental process in the control and modulation of gene expression (Pérez-Ortín et al, 2012). The mRNA degradation process commences with shortening of the poly (A) tail by the Ccr4/Not and Pan2/3 deadenylation complexes. Whereas one pathway can partially substitute for the absence of the other, in yeast most mRNAs are degraded by the decapping-dependent pathway (Beelman et al, 1996; Cao and Parker, 2001; Haimovich et al, 2013; Medina et al, 2014; van Dijk et al, 2011).
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