Dicer - 版本历史

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{{Infobox_gene}}
'''Dicer'''蛋白在人體內由''DICER1''基因編碼，是一種在[[RNA干擾]]中扮演着重要角色的[[RNA酶]]，屬於[[核糖核酸酶Ⅲ|III型RNA酶]]。在[[RNA誘導沉默複合體]]（RISC）的激活中，Dicer扮演着核心角色。在RNA干擾過程中，Dicer可以將[[shRNA]]（小髮卡RNA）切割、加工爲[[siRNA]]（小干擾RNA），將miRNA前體加工爲[[miRNA]]（微RNA）。

==功能==
[[File:MiRNA-biogenesis.jpg|thumb|left|Dicer酶的作用是將shRNA剪切爲siRNA或將miRNA前體剪切爲miRNA]]
Dicer酶會將轉錄而成的、經[[Drosha]]酶初步處理的shRNA（小髮卡RNA）剪切爲siRNA，或將miRNA前體（pre-miRNA）剪切爲miRNA。隨後，siRNA或miRNA會激活RISC的組裝和功能的行使，使RNA干擾得以繼續進行<ref name="Bernstein">{{cite journal |vauthors=Bernstein E, Caudy A, Hammond S, Hannon G |title=Role for a bidentate ribonuclease in the initiation step of RNA interference |url=https://archive.org/details/sim_nature-uk_2001-01-18_409_6818/page/362 |journal=Nature |volume=409 |issue=6818 |pages=363–6 |year=2001 |pmid=11201747 |doi=10.1038/35053110}}</ref>。

==結構==
[[File:2ffl-by-domain.png|thumb|200px|left|肠贾第鞭毛虫（''Giardia intestinalis''）體內的Dicer蛋白。III型RNA酶結構域以綠色標出，PAZ以黃色標出，平臺結構域以紅色標出，連接不同結構域的螺旋以藍色標出<ref name=Macrae_2006>{{cite journal | vauthors = Macrae IJ, Zhou K, Li F, Repic A, Brooks AN, Cande WZ, Adams PD, Doudna JA | title = Structural basis for double-stranded RNA processing by Dicer | url = https://archive.org/details/sim_science_2006-01-13_311_5758/page/194 | journal = Science| volume = 311 | issue = 5758 | pages = 195–8 | date = Jan 2006 | pmid = 16410517 | doi = 10.1126/science.1121638 }}</ref>]]
人DICER蛋白屬於[[核糖核酸酶Ⅲ|III型RNA酶]]，具有解旋酶活性以及PAZ結構域（{{link-en|Piwi|Piwi}}/[[Argonaute]]/Zwille）<ref name="entrez">{{cite web| title = Entrez Gene: DICER1 Dicer1, Dcr-1 homolog (Drosophila)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23405| accessdate = | archive-date = 2019-09-24| archive-url = https://web.archive.org/web/20190924234756/https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=23405| dead-url = no}}</ref><ref name="pmid10786632">{{cite journal | vauthors = Matsuda S, Ichigotani Y, Okuda T, Irimura T, Nakatsugawa S, Hamaguchi M | title = Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase | journal = Biochimica et Biophysica Acta | volume = 1490 | issue = 1-2 | pages = 163–9 | date = Jan 2000 | pmid = 10786632 | doi = 10.1016/S0167-4781(99)00221-3 }}</ref>。除了上述結構域外，DICER蛋白還有兩個RNaseIII結構域和兩個雙鏈RNA結合結構域（DUF283和dsRBD）<ref name = "Hammond_2005">{{cite journal | vauthors = Hammond SM | title = Dicing and slicing: the core machinery of the RNA interference pathway | journal = FEBS Letters | volume = 579 | issue = 26 | pages = 5822–9 | date = Oct 2005 |pmid = 16214139 | doi = 10.1016/j.febslet.2005.08.079 }}</ref>。

目前的研究表明PAZ結構域可以和[[shRNA]]（小髮卡RNA）3'端兩個凸出的核苷酸結合，III型RNA酶結構域則會在dsRNA周圍形成一個假二聚體，啓動核酸鏈的剪切，使shRNA長度逐漸縮短。PAZ結構域和III型RNA酶結構域之間的距離由連接他們的螺旋結構決定，會影響到產生的miRNA/siRNA長度<ref name=Macrae_2006 />。Dicer的dsRBD結構域會與shRNA結合，不過目前並未解析出具體的結合位點。推測認爲dsRBD區可能會與一些調節蛋白（比如人體內的TRBP，果蠅體內的R2D2、Loqs）結合形成複合體，調控RNA酶活性，進而調節終產物的產生<ref name=Cenik_2011>{{cite journal | vauthors = Cenik ES, Fukunaga R, Lu G, Dutcher R, Wang Y, Tanaka Hall TM, Zamore PD | title = Phosphate and R2D2 restrict the substrate specificity of Dicer-2, an ATP-driven ribonuclease | journal = Molecular Cell | volume = 42 | issue = 2 | pages = 172–84 | date = Apr 2011 | pmid = 21419681 | pmc = 3115569 | doi = 10.1016/j.molcel.2011.03.002 }}</ref>。有推測認爲解旋酶結構域會參與對長底物的處理<ref name="Cenik_2011"/>

==參見==
*[[RNA干擾]]
*[[RNA誘導沉默複合體]]

==參考==
{{reflist}}

[[Category:RNA干擾]]