"Degradace RNA v eukaryotech hraje kl\u00ED\u010Dovou \u00FAlohu v\u00A0regulaci genov\u00E9 exprese. Jedn\u00EDm z\u00A0nezbytn\u00FDch faktor\u016F procesov\u00E1n\u00ED a degradace 3 konc\u016F RNA je proteinov\u00FD komplex zvan\u00FD exosom. A\u010Dkoli jeho j\u00E1dro tvo\u0159\u00ED \u0161est potenci\u00E1ln\u00EDch exoribonukle\u00E1z, ani jedna z\u00A0nich si nezachovala enzymatickou aktivitu. Jedinou katalyticky aktivn\u00ED podjednotkou je protein Rrp44p nebo tak\u00E9 Dis3p, jeho\u017E funkce a aktivity byly dosud podrobn\u011B pops\u00E1ny pouze u kvasinek. Sav\u010D\u00ED bu\u0148ky k\u00F3duj\u00ED 3 sekven\u010Dn\u00ED homology kvasinkov\u00E9 Rrp44p: DIS3, DIS3L a DIS3L2. Posledn\u00ED ze zm\u00EDn\u011Bn\u00FDch protein\u016F se zd\u00E1 b\u00FDt nejodli\u0161n\u011Bj\u0161\u00ED, jeliko\u017E postr\u00E1d\u00E1 dom\u00E9nu, kter\u00E1 je v\u00A0kvasinkov\u00E9 Rrp44p zodpov\u00EDd\u00E1 za vazbu na cel\u00FD zbytek exosomu a jej\u00ED absence je let\u00E1ln\u00ED. C\u00EDlem tohoto projektu je detailn\u00ED studium funkce DIS3L2 v\u00A0lidsk\u00FDch tk\u00E1\u0148ov\u00FDch kultur\u00E1ch, charakterizace jeho substr\u00E1tov\u00E9ho reperto\u00E1ru RNA a biochemick\u00E1 charakterizace enzymatick\u00FDch a vazebn\u00FDch aktivit na RNA. Vzhledem ke kl\u00ED\u010Dov\u00E9 \u00FAloze Rrp44p v\u00A0kvasink\u00E1ch p\u0159edpokl\u00E1d\u00E1me, \u017Ee ka\u017Ed\u00FD ze t\u0159\u00ED zm\u00EDn\u011Bn\u00FDch homolog\u016F bude m\u00EDt v\u00FDznamnou \u00FAlohu na bun\u011B\u010Dn\u00E9 i organism\u00E1ln\u00ED \u00FArovni u savc\u016F." . . "2014-12-31+01:00"^^ . . "2014-04-18+02:00"^^ . "2011-01-01+01:00"^^ . . "Functional and biochemical characterization of Dis3L2, the third mammalian homolog of the key yeast exosome nuclease Dis3p"@en . "The project was fulfilled in an excellent way and yielded important new knowledge on the role of DIS3L2 as an exonuclease specifically targeting uridylated microRNA, revealing the role of uridinylation in the metabolism of RNA in the cell. The tree published papers (in high quality journals like Genes & Development, Nucleic Acids Research, RNA) received high attention of the research community."@en . . "Projekt byl spln\u011Bn skv\u011Bl\u00FDm zp\u016Fsobem a byly z\u00EDsk\u00E1ny v\u00FDznamn\u00E9 v\u00FDsledky. Byla odhalena aktivita DIS3L2 jako exonukle\u00E1zy specificky targetuj\u00EDc\u00ED uridylovan\u00E9 formy microRNA a dal\u0161\u00ED v\u00FDsledky ukazuj\u00ED na v\u00FDznamnou roli uridylace v metabolismu RNA a fyziologii bu\u0148ky. Byly ji\u017E publikov\u00E1ny 3 v\u00FDznamn\u00E9 pr\u00E1ce ve vynikaj\u00EDc\u00EDch \u010Dasopisech a dal\u0161\u00ED je v revizi pro Nucleic acid Research."@cs . . . . "4"^^ . "0"^^ . . . "4"^^ . . . "1"^^ . . "2015-05-22+02:00"^^ . . "Funk\u010Dn\u00ED a biochemick\u00E1 charakterizace proteinu Dis3L2, t\u0159et\u00EDho lidsk\u00E9ho homologu hlavn\u00ED kvasinkov\u00E9 exosomov\u00E9 nukle\u00E1zy Dis3p" . . . . "GAP305/11/1095" . . "http://www.isvav.cz/projectDetail.do?rowId=GAP305/11/1095"^^ . "0"^^ . . "\u00A0RNA trimming and turnover plays a key role in eukaryotic gene expression regulation. The degradation and trimming at RNA 3-prime ends is catalyzed by an essential protein complex called the exosome. Although, the exosome core includes six potential exoribonucleases, none of them is catalytically active. The main and only active component is the tenth subunit Rrp44p/Dis3p. Its function and activities have only been described in detail in yeast. Mammalian cells encode three Rrp44p sequence homologs; DIS3, DIS3L and DIS3L2. DIS3L2 is the least similar because it lacks the PIN domain, which is in yeast responsible for binding the exosome core and is essential for viability. The aim of this proposal is to investigate in detail DIS3L2 function in human cells, to characterize the RNA substrate repertoir and to describe the biochemical properties such as enzymatic activities and RNA affinity. In regard to the role of Rrp44p in yeast we expect that all three human homologs will have essential roles for cell and organism function in mammals."@en . "RNA degradation 3' to 5' exonuclease Rrp44p Dis3p exosome"@en . . .