Dicer

DICER酶
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	2EB1、4NGB、4NGC、4NGD、4NGF、4NGG、4NH3、4NH5、4NH6、4NHA、4WYQ
識別號
別名	DICER1；, DCR1, Dicer, Dicer1e, HERNA, MNG1, RMSE2, K12H4.8-LIKE, dicer 1, ribonuclease III, GLOW
外部ID	OMIM：606241 MGI：2177178 HomoloGene：13251 GeneCards：DICER1
相關疾病
	胸膜肺母細胞瘤、胚胎性橫紋肌肉瘤、DICER1 syndrome、familial multinodular goiter
基因位置（人類）
染色體	14號染色體
終止	95,158,010 bp
基因位置（小鼠）
染色體	小鼠12號染色體
終止	104,718,211 bp
基因本體
分子功能	• 核苷酸結合; • helicase activity; • protein domain specific binding; • pre-miRNA binding; • 金屬離子結合; • endoribonuclease activity; • endoribonuclease activity, producing 5'-phosphomonoesters; • 血漿蛋白結合; • siRNA binding; • RNA binding; • nuclease activity; • double-stranded RNA binding; • endonuclease activity; • 水解酶活性; • ATP結合; • ribonuclease III activity; • DNA結合; • deoxyribonuclease I activity;
細胞組分	• 細胞質; • 細胞質基質; • RNA誘導沉默複合體; • 生長錐; • ARC complex; • RISC-loading complex; • 軸突; • 樹突; • 細胞核; • endoplasmic reticulum-Golgi intermediate compartment; • 外排體;
生物學過程	• neuron projection morphogenesis; • RNA processing; • negative regulation of transcription by RNA polymerase II; • peripheral nervous system myelin formation; • pre-miRNA processing; • positive regulation of myelination; • nerve development; • RNA phosphodiester bond hydrolysis, endonucleolytic; • positive regulation of Schwann cell differentiation; • negative regulation of Schwann cell proliferation; • production of miRNAs involved in gene silencing by miRNA; • miRNA metabolic process; • production of siRNA involved in RNA interference; • 基因沉默; • apoptotic DNA fragmentation; • 腫瘤壞死因子產生的負調控; • NIK/NF-kappaB signaling; • negative regulation of gene expression; • tube formation;
	Sources:Amigo / QuickGO
直系同源
	23405
	192119
	ENSG00000100697
	ENSMUSG00000041415
	Q9UPY3
	Q8R418,F8VQ54
	NM_001195573; NM_001271282; NM_001291628; NM_030621; NM_177438
	NM_148948
	NP_001182502; NP_001258211; NP_001278557; NP_085124; NP_803187
	NP_683750
	維基數據
檢視/編輯人類	檢視/編輯小鼠

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

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^[6]。

結構

腸賈第鞭毛蟲（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^[7]

人DICER蛋白屬於III型RNA酶，具有解旋酶活性以及PAZ結構域（Piwi（英語：Piwi）/Argonaute/Zwille）^[8]^[9]。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）^[10]。

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^[7]。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^[11]。有推測認爲解旋酶結構域會參與對長底物的處理^[11]

參見

參考

^ 與DICER酶相關的疾病；在維基數據上查看/編輯參考.
^ ^2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000100697 - Ensembl, May 2017
^ ^3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000041415 - Ensembl, May 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.
^ Bernstein E, Caudy A, Hammond S, Hannon G. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001, 409 (6818): 363–6. PMID 11201747. doi:10.1038/35053110.
^ ^7.0 ^7.1 Macrae IJ, Zhou K, Li F, Repic A, Brooks AN, Cande WZ, Adams PD, Doudna JA. Structural basis for double-stranded RNA processing by Dicer. Science. Jan 2006, 311 (5758): 195–8. PMID 16410517. doi:10.1126/science.1121638.
^ Entrez Gene: DICER1 Dicer1, Dcr-1 homolog (Drosophila). （原始內容存檔於2019-09-24）.
^ Matsuda S, Ichigotani Y, Okuda T, Irimura T, Nakatsugawa S, Hamaguchi M. Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase. Biochimica et Biophysica Acta. Jan 2000, 1490 (1-2): 163–9. PMID 10786632. doi:10.1016/S0167-4781(99)00221-3.
^ Hammond SM. Dicing and slicing: the core machinery of the RNA interference pathway. FEBS Letters. Oct 2005, 579 (26): 5822–9. PMID 16214139. doi:10.1016/j.febslet.2005.08.079.
^ ^11.0 ^11.1 Cenik ES, Fukunaga R, Lu G, Dutcher R, Wang Y, Tanaka Hall TM, Zamore PD. Phosphate and R2D2 restrict the substrate specificity of Dicer-2, an ATP-driven ribonuclease. Molecular Cell. Apr 2011, 42 (2): 172–84. PMC 3115569  . PMID 21419681. doi:10.1016/j.molcel.2011.03.002.

[1] 與DICER酶相關的疾病；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000100697 - Ensembl, May 2017

[refGRCm38Ensembl-3] 3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000041415 - Ensembl, May 2017

[4] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[Bernstein-6] Bernstein E, Caudy A, Hammond S, Hannon G. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001, 409 (6818): 363–6. PMID 11201747. doi:10.1038/35053110.

[Macrae_2006-7] 7.0 ^7.1 Macrae IJ, Zhou K, Li F, Repic A, Brooks AN, Cande WZ, Adams PD, Doudna JA. Structural basis for double-stranded RNA processing by Dicer. Science. Jan 2006, 311 (5758): 195–8. PMID 16410517. doi:10.1126/science.1121638.

[entrez-8] Entrez Gene: DICER1 Dicer1, Dcr-1 homolog (Drosophila). （原始內容存檔於2019-09-24）.

[pmid10786632-9] Matsuda S, Ichigotani Y, Okuda T, Irimura T, Nakatsugawa S, Hamaguchi M. Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase. Biochimica et Biophysica Acta. Jan 2000, 1490 (1-2): 163–9. PMID 10786632. doi:10.1016/S0167-4781(99)00221-3.

[Hammond_2005-10] Hammond SM. Dicing and slicing: the core machinery of the RNA interference pathway. FEBS Letters. Oct 2005, 579 (26): 5822–9. PMID 16214139. doi:10.1016/j.febslet.2005.08.079.

[Cenik_2011-11] 11.0 ^11.1 Cenik ES, Fukunaga R, Lu G, Dutcher R, Wang Y, Tanaka Hall TM, Zamore PD. Phosphate and R2D2 restrict the substrate specificity of Dicer-2, an ATP-driven ribonuclease. Molecular Cell. Apr 2011, 42 (2): 172–84. PMC 3115569  . PMID 21419681. doi:10.1016/j.molcel.2011.03.002.

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