The mitogen-activated protein kinase Slt2 regulates nuclear retention of non-heat shock mRNAs during heat shock-induced stress.
Cellular adaptation to environmental stress conditions requires rapid and specific changes in gene expression. During heat shock, most polyadenylated mRNAs are retained in the nucleus, whereas the export of heat shock-induced mRNAs is allowed. Although essential mRNA export factors are known, the precise mechanism for regulating transport is not fully understood. Here we find that during heat shock in Saccharomyces cerevisiae, the mRNA-binding protein Nab2 is phosphorylated on threonine 178 and serine 180 by the mitogen-activated protein (MAP) kinase Slt2/Mpk1. Slt2 is required for nuclear poly(A(+)) mRNA accumulation upon heat shock, and thermotolerance is decreased in a nup42 nab2-T178A/S180A mutant. Coincident with phosphorylation, Nab2 and Yra1 colocalize in nuclear foci with Mlp1, a protein involved in mRNA retention. Nab2 nuclear focus formation and Nab2 phosphorylation are independent, suggesting that heat shock induces multiple cellular alterations that impinge upon transport efficiency. Under normal conditions, we find that the mRNA export receptor Mex67 and Nab2 directly interact. However, upon heat shock stress, Mex67 does not localize to the Mlp1 nuclear foci, and its association with Nab2 complexes is reduced. These results reveal a novel mechanism by which the MAP kinase Slt2 and Mlp1 control mRNA export factors during heat shock stress.
Carmody
Sean R
SR
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232-8240, USA.
Tran
Elizabeth J
EJ
Apponi
Luciano H
LH
Corbett
Anita H
AH
Wente
Susan R
SR
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D005800:Genes, Fungal; D018869:Heat-Shock Response / Q000235:genetics / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C106898:MEX67 protein, S cerevisiae; C080988:MLP1 protein, S cerevisiae; C080773:NAB2 protein, S cerevisiae; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C105887:YRA1 protein, S cerevisiae; C072075:BCK1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae; D020929:Mitogen-Activated Protein Kinase Kinases
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