Heterogeneous ribonucleoprotein particle - Wikipedia

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are complexes of RNA ; hnRNPs are also integral to the 40s ; The proteins involved in the hnRNP complexes are ... Heterogeneousribonucleoproteinparticle FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch Heterogeneousnuclearribonucleoproteins(hnRNPs)arecomplexesofRNAandproteinpresentinthecellnucleusduringgenetranscriptionandsubsequentpost-transcriptionalmodificationofthenewlysynthesizedRNA(pre-mRNA).Thepresenceoftheproteinsboundtoapre-mRNAmoleculeservesasasignalthatthepre-mRNAisnotyetfullyprocessedandthereforenotreadyforexporttothecytoplasm.[1]SincemostmatureRNAisexportedfromthenucleusrelativelyquickly,mostRNA-bindingproteininthenucleusexistasheterogeneousribonucleoproteinparticles.Aftersplicinghasoccurred,theproteinsremainboundtosplicedintronsandtargetthemfordegradation. hnRNPsarealsointegraltothe40ssubunitoftheribosomeandthereforeimportantforthetranslationofmRNAinthecytoplasm.[2]However,hnRNPsalsohavetheirownnuclearlocalizationsequences(NLS)andarethereforefoundmainlyinthenucleus.ThoughitisknownthatafewhnRNPsshuttlebetweenthecytoplasmandnucleus,immunofluorescencemicroscopywithhnRNP-specificantibodiesshowsnucleoplasmiclocalizationoftheseproteinswithlittlestaininginthenucleolusorcytoplasm.[3]ThisislikelybecauseofitsmajorroleinbindingtonewlytranscribedRNAs.High-resolutionimmunoelectronmicroscopyhasshownthathnRNPslocalizepredominantlytotheborderregionsofchromatin,whereithasaccesstothesenascentRNAs.[4] TheproteinsinvolvedinthehnRNPcomplexesarecollectivelyknownasheterogeneousribonucleoproteins.TheyincludeproteinKandpolypyrimidinetract-bindingprotein(PTB),whichisregulatedbyphosphorylationcatalyzedbyproteinkinaseAandisresponsibleforsuppressingRNAsplicingataparticularexonbyblockingaccessofthespliceosometothepolypyrimidinetract.[5]: 326 hnRNPsarealsoresponsibleforstrengtheningandinhibitingsplicesitesbymakingsuchsitesmoreorlessaccessibletothespliceosome.[6]CooperativeinteractionsbetweenattachedhnRNPsmayencouragecertainsplicingcombinationswhileinhibitingothers.[7] Contents 1RoleincellcycleandDNAdamage 1.1BRCA1 1.2HER2 1.3p53 2Functions 2.1CD44Regulation 2.2Telomeres 3Examples 4Seealso 5References 6Furtherreading RoleincellcycleandDNAdamage[edit] hnRNPsaffectseveralaspectsofthecellcyclebyrecruiting,splicing,andco-regulatingcertaincellcyclecontrolproteins.MuchofhnRNPs'importancetocellcyclecontrolisevidencedbyitsroleasanoncogene,inwhichalossofitsfunctionsresultsinvariouscommoncancers.Often,misregulationbyhnRNPsisduetosplicingerrors,butsomehnRNPsarealsoresponsibleforrecruitingandguidingtheproteinsthemselves,ratherthanjustaddressingnascentRNAs. BRCA1[edit] hnRNPCisakeyregulatoroftheBRCA1andBRCA2genes.Inresponsetoionizingradiation,hnRNPCpartiallylocalizestothesiteofDNAdamage,andwhendepleted,S-phaseprogressionofthecellisimpaired.[8]Additionally,BRCA1andBRCA2levelsfallwhenhnRNPCislost.BRCA1andBRCA2arecrucialtumor-suppressorgeneswhicharestronglyimplicatedinbreastcancerswhenmutated.BRCA1inparticularcausesG2/McellcyclearrestinresponsetoDNAdamageviatheCHEK1signalingcascade.[9]hnRNPCisimportantfortheproperexpressionofothertumorsuppressorgenesincludingRAD51andBRIP1aswell.Throughthesegenes,hnRNPisnecessarytoinducecell-cyclearrestinresponsetoDNAdamagebyionizingradiation.[7] HER2[edit] HER2isoverexpressedin20-30%ofbreastcancersandiscommonlyassociatedwithpoorprognosis.Itisthereforeanoncogenewhosedifferentlysplicedvariantshavebeenshowntohavedifferentfunctions.KnockingdownhnRNPH1wasshowntoincreasetheamountofanoncogenicvariantΔ16HER2.[10]HER2isanupstreamregulatorofcyclinD1andp27,anditsoverexpressionleadstothederegulationoftheG1/Scheckpoint.[11] p53[edit] hnRNPsalsoplayaroleinDNAdamageresponseincoordinationwithp53.hnRNPKisrapidlyinducedafterDNAdamagebyionizingradiation.Itcooperateswithp53toinducetheactivationofp53targetgenes,thusactivatingcell-cyclecheckpoints.[12]p53itselfisanimportanttumor-suppressorgenesometimesknownbytheepithet“theguardianofthegenome.”hnRNPK’scloseassociationwithp53demonstratesitsimportanceinDNAdamagecontrol. p53regulatesalargegroupofRNAsthatarenottranslatedintoprotein,calledlargeintergenicnoncodingRNAs(lincRNAs).p53suppressionofgenesisoftencarriedoutbyanumberoftheselincRNAs,whichinturnhavebeenshowntoactthoughhnRNPK.Throughphysicalinteractionswiththesemolecules,hnRNPKistargetedtogenesandtransmitsp53regulation,thusactingasakeyrepressorwithinthep53-dependenttranscriptionalpathway.[13][14] Functions[edit] hnRNPservesavarietyofprocessesinthecell,someofwhichinclude: Preventingthefoldingofpre-mRNAintosecondarystructuresthatmayinhibititsinteractionswithotherproteins. Possibleassociationwiththesplicingapparatus. TransportofmRNAoutofthenucleus. Theassociationofapre-mRNAmoleculewithahnRNPparticlepreventsformationofshortsecondarystructuresdependentonbasepairingofcomplementaryregions,therebymakingthepre-mRNAaccessibleforinteractionswithotherproteins. CD44Regulation[edit] hnRNPhasbeenshowntoregulateCD44,acell-surfaceglycoprotein,throughsplicingmechanisms.CD44isinvolvedincell-cellinteractionsandhasrolesincelladhesionandmigration.SplicingofCD44andthefunctionsoftheresultingisoformsaredifferentinbreastcancercells,andwhenknockeddown,hnRNPreducedbothcellviabilityandinvasiveness.[15] Telomeres[edit] SeveralhnRNPsinteractwithtelomeres,whichprotecttheendsofchromosomesfromdeteriorationandareoftenassociatedwithcelllongevity.hnRNPDassociateswiththeG-richrepeatregionofthetelomeres,possiblystabilizingtheregionfromsecondarystructureswhichwouldinhibittelomerereplication.[16] hnRNPhasalsobeenshowntointeractwithtelomerase,theproteinresponsibleforelongatingtelomeresandpreventtheirdegradation.hnRNPsC1andC2associatewiththeRNAcomponentoftelomerase,whichimprovesitsabilitytoaccessthetelomere.[17][18][19] Examples[edit] Humangenesencodingheterogeneousnuclearribonucleoproteinsinclude: HNRNPA0,HNRNPA1,HNRNPA1L1,HNRNPA1L2,HNRNPA3,HNRNPA2B1 HNRNPAB HNRNPB1 HNRNPC,HNRNPCL1 HNRNPD(AUF1),HNRPDL HNRNPF HNRNPG(RBMX) HNRNPH1,HNRNPH2,HNRNPH3 HNRNPI(PTB) HNRNPK HNRNPL,HNRPLL HNRNPM HNRNPP2(FUS/TLS) HNRNPR HNRNPQ(SYNCRIP) HNRNPU,HNRNPUL1,HNRNPUL2,HNRNPUL3 FMR1[20] Seealso[edit] MessengerRNP:complexbetweenmRNAandprotein(s)presentinnucleus References[edit] ^Kinniburgh,A.J.;Martin,T.E.(1976-08-01)."DetectionofmRNAsequencesinnuclear30Sribonucleoproteinsubcomplexes".ProceedingsoftheNationalAcademyofSciences.73(8):2725–2729.Bibcode:1976PNAS...73.2725K.doi:10.1073/pnas.73.8.2725.ISSN 0027-8424.PMC 430721.PMID 1066686. ^Beyer,AnnL.;Christensen,MarkE.;Walker,BarbaraW.;LeStourgeon,WallaceM.(1977)."Identificationandcharacterizationofthepackagingproteinsofcore40ShnRNPparticles".Cell.11(1):127–138.doi:10.1016/0092-8674(77)90323-3.PMID 872217.S2CID 41245800. ^Dreyfuss,Gideon;Matunis,MichaelJ.;Pinol-Roma,Serafin;Burd,ChristopherG.(1993-06-01)."hnRNPProteinsandtheBiogenesisofmRNA".AnnualReviewofBiochemistry.62(1):289–321.doi:10.1146/annurev.bi.62.070193.001445.ISSN 0066-4154.PMID 8352591. ^Fakan,S.;Leser,G.;Martin,T.E.(January1984)."Ultrastructuraldistributionofnuclearribonucleoproteinsasvisualizedbyimmunocytochemistryonthinsections".TheJournalofCellBiology.98(1):358–363.doi:10.1083/jcb.98.1.358.ISSN 0021-9525.PMC 2113018.PMID 6231300. ^MatsudairaPT,LodishHF,BerkA,KaiserC,KriegerM,ScottMP,BretscherA,PloeghH(2008).Molecularcellbiology.SanFrancisco:W.H.Freeman.ISBN 978-0-7167-7601-7. ^Matlin,ArianneJ.;Clark,Francis;Smith,ChristopherW.J.(2005)."Understandingalternativesplicing:towardsacellularcode".NatureReviewsMolecularCellBiology.6(5):386–398.doi:10.1038/nrm1645.ISSN 1471-0080.PMID 15956978.S2CID 14883495. ^abMartinez-Contreras,Rebeca;Cloutier,Philippe;Shkreta,Lulzim;Fisette,Jean-François;Revil,Timothée;Chabot,Benoit(2007).hnRNPproteinsandsplicingcontrol.AdvancesinExperimentalMedicineandBiology.Vol. 623.pp. 123–147.doi:10.1007/978-0-387-77374-2_8.ISBN 978-0-387-77373-5.ISSN 0065-2598.PMID 18380344. ^Anantha,RachelW.;Alcivar,AllenL.;Ma,Jianglin;Cai,Hong;Simhadri,Srilatha;Ule,Jernej;König,Julian;Xia,Bing(2013-04-09)."RequirementofHeterogeneousNuclearRibonucleoproteinCforBRCAGeneExpressionandHomologousRecombination".PLOSONE.8(4):e61368.Bibcode:2013PLoSO...861368A.doi:10.1371/journal.pone.0061368.ISSN 1932-6203.PMC 3621867.PMID 23585894. ^Yoshida,Kiyotsugu;Miki,Yoshio(November2004)."RoleofBRCA1andBRCA2asregulatorsofDNArepair,transcription,andcellcycleinresponsetoDNAdamage".CancerScience.95(11):866–871.doi:10.1111/j.1349-7006.2004.tb02195.x.ISSN 1347-9032.PMID 15546503.S2CID 24297965. ^Gautrey,Hannah;Jackson,Claire;Dittrich,Anna-Lena;Browell,David;Lennard,Thomas;Tyson-Capper,Alison(2015-10-03)."SRSF3andhnRNPH1regulateasplicinghotspotofHER2inbreastcancercells".RNABiology.12(10):1139–1151.doi:10.1080/15476286.2015.1076610.ISSN 1547-6286.PMC 4829299.PMID 26367347. ^Moasser,MM(2007)."TheoncogeneHER2:itssignalingandtransformingfunctionsanditsroleinhumancancerpathogenesis".Oncogene.26(45):6469–6487.doi:10.1038/sj.onc.1210477.ISSN 1476-5594.PMC 3021475.PMID 17471238. ^Moumen,Abdeladim;Masterson,Philip;O'Connor,MarkJ.;Jackson,StephenP.(2005)."hnRNPK:AnHDM2TargetandTranscriptionalCoactivatorofp53inResponsetoDNADamage".Cell.123(6):1065–1078.doi:10.1016/j.cell.2005.09.032.PMID 16360036.S2CID 16756766. ^Huarte,Maite;Guttman,Mitchell;Feldser,David;Garber,Manuel;Koziol,MagdalenaJ.;Kenzelmann-Broz,Daniela;Khalil,AhmadM.;Zuk,Or;Amit,Ido(2010)."ALargeIntergenicNoncodingRNAInducedbyp53MediatesGlobalGeneRepressioninthep53Response".Cell.142(3):409–419.doi:10.1016/j.cell.2010.06.040.PMC 2956184.PMID 20673990. ^Sun,Xinghui;Ali,MohamedShamShihabudeenHaider;Moran,Matthew(2017-09-01)."Theroleofinteractionsoflongnon-codingRNAsandheterogeneousnuclearribonucleoproteinsinregulatingcellularfunctions".BiochemicalJournal.474(17):2925–2935.doi:10.1042/bcj20170280.ISSN 0264-6021.PMC 5553131.PMID 28801479. ^Loh,TiingJen;Moon,Heegyum;Cho,Sunghee;Jang,Hana;Liu,YongChao;Tai,Hongmei;Jung,Da-Woon;Williams,DarrenR.;Kim,Hey-Ran(September2015)."CD44alternativesplicingandhnRNPA1expressionareassociatedwiththemetastasisofbreastcancer".OncologyReports.34(3):1231–1238.doi:10.3892/or.2015.4110.ISSN 1791-2431.PMID 26151392. ^Eversole,A.;Maizels,N.(August2000)."InvitropropertiesoftheconservedmammalianproteinhnRNPDsuggestaroleintelomeremaintenance".MolecularandCellularBiology.20(15):5425–5432.doi:10.1128/mcb.20.15.5425-5432.2000.ISSN 0270-7306.PMC 85994.PMID 10891483. ^Ford,L.P.;Suh,J.M.;Wright,W.E.;Shay,J.W.(December2000)."HeterogeneousnuclearribonucleoproteinsC1andC2associatewiththeRNAcomponentofhumantelomerase".MolecularandCellularBiology.20(23):9084–9091.doi:10.1128/mcb.20.23.9084-9091.2000.ISSN 0270-7306.PMC 86561.PMID 11074006. ^Ford,LanceP.;Wright,WoodringE.;Shay,JerryW.(2002-01-21)."Amodelforheterogeneousnuclearribonucleoproteinsintelomereandtelomeraseregulation".Oncogene.21(4):580–583.doi:10.1038/sj.onc.1205086.ISSN 0950-9232.PMID 11850782. ^Görlach,M.;Burd,C.G.;Dreyfuss,G.(1994-09-16)."ThedeterminantsofRNA-bindingspecificityoftheheterogeneousnuclearribonucleoproteinCproteins".TheJournalofBiologicalChemistry.269(37):23074–23078.doi:10.1016/S0021-9258(17)31621-6.ISSN 0021-9258.PMID 8083209. ^Dityatev,Alexander;El-Husseini,Alaa(2006-11-24).MolecularMechanismsofSynaptogenesis.ISBN 9780387325620. Furtherreading[edit] XieJ,LeeJA,KressTL,MowryKL,BlackDL(July2003)."ProteinkinaseAphosphorylationmodulatestransportofthepolypyrimidinetract-bindingprotein".Proc.Natl.Acad.Sci.U.S.A.100(15):8776–81.Bibcode:2003PNAS..100.8776X.doi:10.1073/pnas.1432696100.PMC 166389.PMID 12851456. GeuensT,DelphineB,TimmermanV(August2016)."ThehnRNPFamily:InsightsintoTheirRoleinHealthandDisease".HumanGenetics.135(8):851–67.doi:10.1007/s00439-016-1683-5.PMC 4947485.PMID 27215579. TakimotoM,TomonagaT,MatunisM,et al.(August1993)."SpecificbindingofheterogeneousribonucleoproteinparticleproteinKtothehumanc-mycpromoter,invitro".J.Biol.Chem.268(24):18249–58.doi:10.1016/S0021-9258(17)46837-2.PMID 8349701.Archivedfromtheoriginalon2019-09-15.Retrieved2009-03-08. Watson,JamesD.(2004).Molecularbiologyofthegene.SanFrancisco:Pearson/BenjaminCummings.pp. ch.9and10.ISBN 978-0-8053-4635-0. vteRNA-bindingprotein:RibonucleoproteinssnRNP A A1 B B2 C D1 D2 D3 E F G N 70K/U1spliceosomalRNA SNRNP200 hnRNP A0 C L R Othertranscription Telomerase Translation Ribosome Vaultribonucleoproteinparticles Majorvaultprotein Other Signalrecognitionparticle Retrievedfrom"https://en.wikipedia.org/w/index.php?title=Heterogeneous_ribonucleoprotein_particle&oldid=1081138864" Categories:GeneexpressionRibonucleoproteins Navigationmenu Personaltools NotloggedinTalkContributionsCreateaccountLogin Namespaces ArticleTalk English Views ReadEditViewhistory More Search Navigation MainpageContentsCurrenteventsRandomarticleAboutWikipediaContactusDonate Contribute HelpLearntoeditCommunityportalRecentchangesUploadfile Tools WhatlinkshereRelatedchangesUploadfileSpecialpagesPermanentlinkPageinformationCitethispageWikidataitem Print/export DownloadasPDFPrintableversion Inotherprojects WikimediaCommons Languages BosanskiČeštinaDeutschEspañolFrançaisGalego日本語PortuguêsไทยTürkçeУкраїнська中文 Editlinks