A Lagorce

AG Hinnebusch

AP Gasch

BJ Breitkreutz

C Berset

D Shenton

D Teixeira

DE Levin

F Gebauer

F Ramirez-Valle

FE Rivera-Molina

FZ Watts

GK Smyth

H Ito

H Martin

J Mata

JA Cruz

JC Varela

JE McCarthy

JF Rodriguez-Quinones

José F Rodríguez-Quiñones

José R Rodríguez-Medina

JR Buchan

JR Rodriguez-Medina

KJ Livak

KM Kuhn

LE Cowen

M Ringner

M Schmidt

Marielis E Rivera-Ruiz

O Donze

P Kafasla

PD Andrews

Pearl Akamine

R Garcia

RC Gentleman

RE Halbeisen

S Izawa

T Powers

TE Dever

VA Cherkasova

VK Mootha

Y Benjamini

Y Sanchez

BMC Genomics

English

PubMed

Springer - Publisher Connector

Post-transcriptional regulation in the myo1Δ mutant of Saccharomyces cerevisiae

Abstract
                Background
                Saccharomyces cerevisiae myosin type II-deficient (myo1 Δ) strains remain viable and divide, despite the absence of a cytokinetic ring, by activation of the PKC1-dependent cell wall integrity pathway (CWIP). Since the myo1 Δ transcriptional fingerprint is a subset of the CWIP fingerprint, the myo1 Δ strain may provide a simplified paradigm for cell wall stress survival.
              
                Results
                To explore the post-transcriptional regulation of the myo1 Δ stress response, 1,301 differentially regulated ribosome-bound mRNAs were identified by microarray analysis of which 204 were co-regulated by transcription and translation. Four categories of mRNA were significantly affected - protein biosynthesis, metabolism, carbohydrate metabolism, and unknown functions. Nine genes of the 20 CWIP fingerprint genes were post-transcriptionally regulated. Down and up regulation of selected ribosomal protein and cell wall biosynthesis mRNAs was validated by their distribution in polysomes from wild type and myo1Δ strains. Western blot analysis revealed accumulation of the phosphorylated form of eukaryotic translation initiation factor 2 (eIF2α-P) and a reduction in the steady state levels of the translation initiation factor eIF4Gp in myo1Δ strains. Deletion of GCN2 in myo1Δ abolished eIF2αp phosphorylation, and showed a severe growth defect. The presence of P-bodies in myo1Δ strains suggests that the process of mRNA sequestration is active, however, the three representative down regulated RP mRNAs, RPS8A, RPL3 and RPL7B were present at equivalent levels in Dcp2p-mCh-positive immunoprecipitated fractions from myo1Δ and wild type cells. These same RP mRNAs were also selectively co-precipitated with eIF2α-P in myo1Δ strains.
              
                Conclusions
                Quantitative analysis of ribosome-associated mRNAs and their polyribosome distributions suggests selective regulation of mRNA translation efficiency in myo1 Δ strains. Inhibition of translation initiation factor eIF2α (eIF2α-P) in these strains was by Gcn2p-dependent phosphorylation. The increase in the levels of eIF2α-P; the genetic interaction between GCN2 and MYO1; and the reduced levels of eIF4Gp suggest that other signaling pathways, in addition to the CWIP, may be important for myo1 Δ strain survival. Selective co-immunoprecipitation of RP mRNAs with eIF2α-P in myo1 Δ strains suggests a novel mode of translational regulation. These results indicate that post-transcriptional control is important in the myo1 Δ stress response and possibly other stresses in yeast.
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Post-transcriptional regulation in the myo1Δ mutant of Saccharomyces cerevisiae

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