Dicer

DICER酶
已知的结构
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	2EB1、4NGB、4NGC、4NGD、4NGF、4NGG、4NH3、4NH5、4NH6、4NHA、4WYQ
识别号
别名	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
相关疾病
	胸膜肺母细胞瘤、胚胎性横纹肌肉瘤、DICER1 syndrome、familial multinodular goiter
基因位置（人类）
染色体	14号染色体
终止	95,158,010 bp
基因位置（小鼠）
染色体	小鼠12号染色体
终止	104,718,211 bp
基因本体
分子功能	• 核苷酸结合; • helicase activity; • protein domain specific binding; • pre-miRNA binding; • 金属离子结合; • endoribonuclease activity; • endoribonuclease activity, producing 5'-phosphomonoesters; • 血浆蛋白结合; • siRNA binding; • RNA binding; • nuclease activity; • double-stranded RNA binding; • endonuclease activity; • 水解酶活性; • ATP结合; • ribonuclease III activity; • DNA结合; • deoxyribonuclease I activity;
细胞组分	• 细胞质; • 细胞质基质; • RNA诱导沉默复合体; • 生长锥; • ARC complex; • RISC-loading complex; • 轴突; • 树突; • 细胞核; • endoplasmic reticulum-Golgi intermediate compartment; • 外排体;
生物学过程	• 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; • 肿瘤坏死因子产生的负调控; • 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
	维基数据
查看/编辑人类	查看/编辑小鼠

Dicer蛋白在人体内由DICER1基因编码，是一种在RNA干扰中扮演着重要角色的RNA酶，属于III型RNA酶。在RNA诱导沉默复合体（RISC）的激活中，Dicer扮演着核心角色。在RNA干扰过程中，Dicer可以将shRNA（小发卡RNA）切割、加工为siRNA（小干扰RNA），将miRNA前体加工为miRNA（微RNA）。

功能编辑

Dicer酶的作用是将shRNA剪切为siRNA或将miRNA前体剪切为miRNA

Dicer酶会将转录而成的、经Drosha酶初步处理的shRNA（小发卡RNA）剪切为siRNA，或将miRNA前体（pre-miRNA）剪切为miRNA。随后，siRNA或miRNA会激活RISC的组装和功能的行使，使RNA干扰得以继续进行^[6]。

结构编辑

肠贾第鞭毛虫（Giardia intestinalis）体内的Dicer蛋白。III型RNA酶结构域以绿色标出，PAZ以黄色标出，平台结构域以红色标出，连接不同结构域的螺旋以蓝色标出^[7]

人DICER蛋白属于III型RNA酶，具有解旋酶活性以及PAZ结构域（Piwi（英语：Piwi）/Argonaute/Zwille）^[8]^[9]。除了上述结构域外，DICER蛋白还有两个RNaseIII结构域和两个双链RNA结合结构域（DUF283和dsRBD）^[10]。

目前的研究表明PAZ结构域可以和shRNA（小发卡RNA）3'端两个凸出的核苷酸结合，III型RNA酶结构域则会在dsRNA周围形成一个假二聚体，启动核酸链的剪切，使shRNA长度逐渐缩短。PAZ结构域和III型RNA酶结构域之间的距离由连接他们的螺旋结构决定，会影响到产生的miRNA/siRNA长度^[7]。Dicer的dsRBD结构域会与shRNA结合，不过目前并未解析出具体的结合位点。推测认为dsRBD区可能会与一些调节蛋白（比如人体内的TRBP，果蝇体内的R2D2、Loqs）结合形成复合体，调控RNA酶活性，进而调节终产物的产生^[11]。有推测认为解旋酶结构域会参与对长底物的处理^[11]

参见编辑

参考编辑

^ 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). （原始内容存档于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). （原始内容存档于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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Dicer

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