DGCR8
Podjedinica DGCR8 mikroprocesorskog kompleksa (kritična regija 8 DiGeorgeovog sindroma) jest protein koji je kod ljudi kodiran genom DGCR8 sa hromosoma 22.[4] Kod drugih životinja, posebno kod običnih modelnih organizama Drosophila melanogaster i Caenorhabditis elegans, protein je poznat kao Pasha (eng. kovanica od partner Drosha).[5] To je obavezna komponenta puta RNK interferencija.
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 773 aminokiseline, а molekulska težina Da. 86 045[6]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| METDESPSPL | PCGPAGEAVM | ESRARPFQAL | PREQSPPPPL | QTSSGAEVMD | ||||
| VGSGGDGQSE | LPAEDPFNFY | GASLLSKGSF | SKGRLLIDPN | CSGHSPRTAR | ||||
| HAPAVRKFSP | DLKLLKDVKI | SVSFTESCRS | KDRKVLYTGA | ERDVRAECGL | ||||
| LLSPVSGDVH | ACPFGGSVGD | GVGIGGESAD | KKDEENELDQ | EKRVEYAVLD | ||||
| ELEDFTDNLE | LDEEGAGGFT | AKAIVQRDRV | DEEALNFPYE | DDFDNDVDAL | ||||
| LEEGLCAPKK | RRTEEKYGGD | SDHPSDGETS | VQPMMTKIKT | VLKSRGRPPT | ||||
| EPLPDGWIMT | FHNSGVPVYL | HRESRVVTWS | RPYFLGTGSI | RKHDPPLSSI | ||||
| PCLHYKKMKD | NEEREQSSDL | TPSGDVSPVK | PLSRSAELEF | PLDEPDSMGA | ||||
| DPGPPDEKDP | LGAEAAPGAL | GQVKAKVEVC | KDESVDLEEF | RSYLEKRFDF | ||||
| EQVTVKKFRT | WAERRQFNRE | MKRKQAESER | PILPANQKLI | TLSVQDAPTK | ||||
| KEFVINPNGK | SEVCILHEYM | QRVLKVRPVY | NFFECENPSE | PFGASVTIDG | ||||
| VTYGSGTASS | KKLAKNKAAR | ATLEILIPDF | VKQTSEEKPK | DSEELEYFNH | ||||
| ISIEDSRVYE | LTSKAGLLSP | YQILHECLKR | NHGMGDTSIK | FEVVPGKNQK | ||||
| SEYVMACGKH | TVRGWCKNKR | VGKQLASQKI | LQLLHPHVKN | WGSLLRMYGR | ||||
| ESSKMVKQET | SDKSVIELQQ | YAKKNKPNLH | ILSKLQEEMK | RLAEEREETR | ||||
| KKPKMSIVAS | AQPGGEPLCT | VDV |
Funkcija
urediPodjedinica DGCR8 je nalazi se u ćelijskom jedru i potrebna je za preradu mikroRNK (miRNA). Veže se za drugu podjedinicu Drosha, enzima RNaza III da bi formirao mikroprocesorski kompleks koji cijepa primarni transkript poznat kao pri-miRNK na karakterističnoj strukturu matična petlja poznatoj kao pre-miRNK, koja se zatim dalje obrađuje u fragmente miRNK pomoću enzima Dicer. DGCR8 sadrži RNK-vezujući domen i smatra se da veže pri-miRNK, kako bi je stabilizirala za obradu pomoću Drosha.[7]
DGCR8 je takođe potreban za neke tipove popravke DNK. Uklanjanje UV-indukovane DNK fotoprodukata, tokom transkripcije ekscizijskog popravka (TC-NER), spojenih nukleotidna što zavisi od JNK fosforilacije DGCR8 na serinu 153.[8] Iako je poznato da DGCR8 funkcionira u biogenezi mikroRNK, ova aktivnost nije potrebna za uklanjanje fotoproizvoda uzrokovanih UV- zračenjem ovisno o DGCR8.[8] Nukleotidni popravak ekscizijom također je potreban za popravak oksidativnog oštećenja DNK zbog na vodik-peroksida (H2O2), a osiromašene ćelije u DGCR8 osjetljive su na H2O2.[8]
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000128191 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: DGCR8 DiGeorge syndrome critical region gene 8".
- ^ Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ (Nov 2004). "Processing of primary microRNAs by the Microprocessor complex". Nature. 432 (7014): 231–5. doi:10.1038/nature03049. PMID 15531879.
- ^ "UniProt, Q8WYQ5" (jezik: engleski). Pristupljeno 2. 11. 2021.
- ^ Yeom KH, Lee Y, Han J, Suh MR, Kim VN (2006). "Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing". Nucleic Acids Research. 34 (16): 4622–9. doi:10.1093/nar/gkl458. PMC 1636349. PMID 16963499.
- ^ a b c Calses PC, Dhillon KK, Tucker N, Chi Y, Huang JW, Kawasumi M, Nghiem P, Wang Y, Clurman BE, Jacquemont C, Gafken PR, Sugasawa K, Saijo M, Taniguchi T (2017). "DGCR8 Mediates Repair of UV-Induced DNA Damage Independently of RNA Processing". Cell Rep. 19 (1): 162–174. doi:10.1016/j.celrep.2017.03.021. PMC 5423785. PMID 28380355.
Dopunska literatura
uredi- Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (Sep 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
- Shiohama A, Sasaki T, Noda S, Minoshima S, Shimizu N (Apr 2003). "Molecular cloning and expression analysis of a novel gene DGCR8 located in the DiGeorge syndrome chromosomal region". Biochemical and Biophysical Research Communications. 304 (1): 184–90. doi:10.1016/S0006-291X(03)00554-0. PMID 12705904.
- Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R (Nov 2004). "The Microprocessor complex mediates the genesis of microRNAs". Nature. 432 (7014): 235–40. doi:10.1038/nature03120. PMID 15531877.
- Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN (Dec 2004). "The Drosha-DGCR8 complex in primary microRNA processing". Genes & Development. 18 (24): 3016–27. doi:10.1101/gad.1262504. PMC 535913. PMID 15574589.
- Landthaler M, Yalcin A, Tuschl T (Dec 2004). "The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis". Current Biology. 14 (23): 2162–7. doi:10.1016/j.cub.2004.11.001. hdl:11858/00-001M-0000-0012-EB83-3. PMID 15589161.
- Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN (Jun 2006). "Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex". Cell. 125 (5): 887–901. doi:10.1016/j.cell.2006.03.043. PMID 16751099.
- Faller M, Matsunaga M, Yin S, Loo JA, Guo F (Jan 2007). "Heme is involved in microRNA processing". Nature Structural & Molecular Biology. 14 (1): 23–9. doi:10.1038/nsmb1182. PMID 17159994.
- Sohn SY, Bae WJ, Kim JJ, Yeom KH, Kim VN, Cho Y (Sep 2007). "Crystal structure of human DGCR8 core". Nature Structural & Molecular Biology. 14 (9): 847–53. doi:10.1038/nsmb1294. PMID 17704815.