Sequestration of Highly Expressed mRNAs in Cytoplasmic Granules, P-Bodies, and Stress Granules Enhances Cell Viability 英文参考文献.docVIP

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Sequestration of Highly Expressed mRNAs in Cytoplasmic Granules, P-Bodies, and Stress Granules Enhances Cell Viability 英文参考文献.doc

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Sequestration of Highly Expressed mRNAs in Cytoplasmic Granules, P-Bodies, and Stress Granules Enhances Cell Viability 英文参考文献

SequestrationofHighlyExpressedmRNAsin CytoplasmicGranules,P-Bodies,andStressGranules EnhancesCellViability AnnaLavut,DinaRaveh* DepartmentofLifeSciences,BenGurionUniversityoftheNegev,Beersheba,Israel Abstract Transcriptomeanalysesindicatethatacore10%–15%oftheyeastgenomeismodulatedbyavarietyofdifferentstresses. However,notalltheinducedgenesundergotranslation,andnullmutantsofmanyinducedgenesdonotshowelevated sensitivity to the particular stress. Elucidation of the RNA lifecycle reveals accumulation of non-translating mRNAs in cytoplasmicgranules,P-bodies,andstressgranulesforfutureregulation.P-bodiescontainenzymesformRNAdegradation; under stress conditions mRNAs may be transferred to stress granules for storage and return to translation. Protein degradationbytheubiquitin-proteasomesystemiselevatedbystress;andhereweanalyzedthesteadystatelevels,decay, andsubcellularlocalizationofthemRNAofthegeneencodingtheF-boxprotein,UFO1,thatisinducedbystress.Usingthe MS2L mRNA reporter system UFO1 mRNA was observed in granules that colocalized with P-bodies and stress granules. TheseP-bodiesstoreddiversemRNAs.GranulesoftwomRNAstransportedpriortotranslation,ASH1-MS2LandOXA1-MS2L, dockedwithP-bodies. HSP12mRNAthatgaverisetohighlyelevatedproteinlevelswasnotobservedingranulesunder these stress conditions. ecd3, pat1 double mutants that are defective in P-body formation were sensitive to mRNAs expressedectopicallyfromstrongpromoters.ThesehighlyexpressedmRNAsshowedelevatedtranslationcomparedwith wild-typecells,andtheviabilityofthemutantswasstronglyreduced.ecd3,pat1mutantsalsoexhibitedincreasedsensitivity todifferentstresses.OurinterpretationisthatsequestrationofhighlyexpressedmRNAsinP-bodiesisessentialforviability. StorageofmRNAsforfutureregulationmaycontributetothediscrepancybetweenthesteadystatelevelsofmanystress- induced mRNAs and their proteins. Sorting of mRNAs for future translation or decay by individual cells could generate potentiallydifferentphenotypesinageneticallyidenticalpop