Beyond the Transcripts What Controls Protein Variation.docVIP

Synopsis BeyondtheTranscripts:WhatControlsProteinVariation? LauraStraub* FreelanceScienceWriter,Arlington,Virginia,UnitedStatesofAmerica Itwaslongthoughtthatifyouknewthe contents ofthe genome, andwhichgenes madewhichproteins,youwouldknowthe basicinstructionsforbuildinganorganism andalltheprocessesitneedstostayalive. underlying transcripts and found over- whelming evidence to the contrary. In- stead, their results point to regulatory mechanisms unrelated to transcriptional control as the ultimate determiners of proteomevariationinageneticallydiverse population. Organisms convert extensive genomic instructions into a specific protein reper- toireviatranscriptionandtranslation.It’s clearthattheactoftranscriptionistightly controlledbythecell,andscientistshavea relatively good grasp of the mechanisms thatregulategeneexpression.Asaresult, we tend to have a rather ‘‘transcript- centric’’ view of biology, assuming that more transcript automatically translates into more proteins. This is the tacit premise underlying countless gene-tran- scription studies in which levels of thou- sandsoftranscriptsaremeasuredundera rangeofconditionsandtheresultshappily extrapolated to their protein products. Notionally,however,thisisnotnecessarily thecase,becausedownstreamcontrolson translation, protein folding, and protein degradation have the potential to trump theimpactofearliertranscriptionalactiv- ity. To explore the relationship between and corresponding protein transcripts levels,theresearchersusedhighlysensitive methods to simultaneously measure levels of proteins and their transcripts in 95 genetically distinct yeaststrains. Usingan enhancedversionofanalgorithmtheyhad previously developed to measure protein levels, they reanalyzed an existing mass spectrometry–based dataset and obtained moreaccurateanddetailedresultsfor354 high-abundance proteins—twice as many astheyhadpreviouslymeasured.Ofnote, thecorrespondingtranscriptsforthese354 proteins wereamongthosewith themost variab