lecture25

In our discussion, we will put genes into three categories based on their regulation: constitutive genes, inducible genes, and silenced genes. 9March 2005 Lecture25 Reading:Chapter 8 VI.Genes A.Proteinsynthesis(TheCentral Dogma) B.Genomes C.Generegulation Theactivity,i.e.transcription,of genesishighlyregulated.Inourdiscussion,wewillputgenesinto threecategoriesbasedontheirregulation:constitutivegenes, induciblegenes,andsilencedgenes.Constitutivegenesarethose thatarealwaysactive.Genesforribosomesareanexample.Theyare constantlybeingtranscribedbecauseribosomesareconstantlyneeded forproteinsynthesis.Induciblegenesarethosethathavevariable activity,dependingontheneedsofthecell.Forexample,the glucosetransporterproteinsthatmusclecellsproduceinresponseto insulinaretheproductofinduciblegenes.Insulinstimulatestheir activity.Silencedgenesarethosethathavebeenpermanentlyturned off.Forexample,somegenesneededfornervecellfunctionwillbe silencedinmusclecells.Genesilencingispartoftheprocessof cellsaquiringtheirdifferentidentities. 1.Promotersandtranscriptional regulation Geneshavedifferentparts.The sequenceofbasesthatcodesforaminoacidsinaproteinisjustone ofthese.Anotherpartofallgenesisthepromoter.Thisisa segmentofDNAupstreamfromtheregionthatistranscribedinto messengerRNA.ItisthepartofthegenewhereRNApolymerasebinds andbeginscopyingthegenesequenceintomessengerRNA. Transcriptionofgenesiscontrolled byproteinsthatbindonornearthepromoter.Someproteinswill favorthebindingofRNApolymeraseandtherebytranscriptionofthe gene.OtherproteinswillpreventthebindingofRNApolymeraseand thuspreventtranscriptionofthegene.Theseproteinsarecalled "generegulatoryproteins".(Youwillseethemcalledtranscription factorsandregulatoryproteinsinyourtextandtherearemanyother namesforthem,dependingonwhattheproteindoes.Wewillcallthem all"generegulatoryproteins").Generegulatoryproteinsarecoded forby"regulatorygenes".Generegulatoryproteinsoftenbindto morethanonegene,whichmeansthataregulatorygenecan simultaneouslygoverntheactivityofsetsofgenes. Somegeneregulatoryproteinsbindto placesotherthanthepromoterofagenebutstillaffectits transcription.Forexample,someproteinsbindto"enhancers",which areregionsofDNAthatarehundredsofbasesupstreamfromthe promoter.Itisthoughtthattheseregionsmaylooparoundsothat theyinteractwiththepromoterandimprovebindingofRNApolymerase fortranscription.   2.Introns,exons,andalternative splicing Withintheregionofagenethatis transcribedintomessengerRNA,therearesegmentsofDNAthatdonot codeforaminoacidsequence.Thesesegmentsarecalled"introns", whichisshortfor"interveningsequences".Thepartsofthegene sequencethatdogettranslatedintoaminoacidsequencearecalled "exons".ExonsandintronsalikearecopiedintomessengerRNAbyRNA polymerasebuttheintronsarecutoutbyeditingenzymesbeforethe messengerRNAleavesthenucleus.Theintronsequencesarecutoutof themessengerRNAmoleculeandtheexonsarespliced together. Sometimes,exonsfromageneare splicedtogetherinseveraldifferentways,leadingtodifferent kindsofproteins.Thisprocessiscalled"alternativesplicing". Alternativesplicingisameansbywhichgenescanberegulatedafter transcriptionoccurs.Itisalsoawayforcellstomakemore proteinsthantheyhavegenes.Asproteinsynthesiswasbeing studied,ahypothesiswasproposedthatonegenecodedforone protein.Thisisgenerallytruebutalternativesplicingisone exceptiontothisrule.