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Drosha

本页使用了标题或全文手工转换
维基百科,自由的百科全书
Drosha酶
已知的結構
PDB直系同源搜索: PDBe RCSB
識別號
别名DROSHA;, ETOHI2, HSA242976, RANSE3L, RN3, RNASE3L, RNASEN, drosha ribonuclease III
外部IDOMIM608828 MGI1261425 HomoloGene8293 GeneCardsDROSHA
基因位置(人类
5號染色體
染色体5號染色體[1]
5號染色體
Drosha酶的基因位置
Drosha酶的基因位置
基因座5p13.3起始31,400,494 bp[1]
终止31,532,196 bp[1]
RNA表达模式
查阅更多表达数据
直系同源
物種人類小鼠
Entrez
Ensembl
UniProt
mRNA​序列

NM_001100412
​NM_013235
​NM_001382508

NM_001130149
​NM_026799

蛋白序列

NP_001093882
​NP_037367
​NP_001369437

NP_001123621
​NP_081075

基因位置​(UCSC)Chr 5: 31.4 – 31.53 MbChr 15: 12.82 – 12.94 Mb
PubMed​查找[3][4]
維基數據
檢視/編輯人類檢視/編輯小鼠

Drosha是一種RNA酶III[5],在人類基因組中由5號染色體上的DROSHA基因(舊稱RNASEN)編碼[6][7][8],於2000年被克隆發表,最初被發現為切割rRNA前驅物(pre-rRNA)的一種RNA酶[9],現已知其主要功能為在miRNA生成的初期切割miRNA的前驅物,此蛋白可與DGCR8蛋白組成微加工复合体英语Microprocessor complex[10],將DNA轉錄產生的pri-miRNA切割成長約70nt的pre-miRNA,後者可再由Dicer切割產生成熟的miRNA[11]。Drosha、Dicer與其他參與miRNA生成的蛋白之表現量與某些癌症相關[12]

功能

miRNA生成過程與RNA干擾示意圖
Drosha與兩個DGCR8組成的微加工复合体結構

RNA酶III皆為切割雙股RNA的RNA內切酶,其中Drosha在細胞核中參與miRNA前驅物切割的初始步驟[8][11]。miRNA的生成過程最初是由RNA聚合酶II轉錄產生可長達數kb、具5′端帽多腺苷酸尾初級轉錄本英语primary transcriptpri-miRNA(初級miRNA)[13][14],其受Drosha切割後會形成長約70nt、且3′端具2個突出鹼基(overhang)的pre-miRNA(前miRNA)。pre-miRNA可與XPO5英语XPO5蛋白結合,由細胞核被送入細胞質中,其3′端的突出鹼基可被另一種RNA酶IIIDicer所識別,後者可再將pre-miRNA切割成長22nt的雙股RNA,其中的一股即是成熟的miRNA,可與RNA誘導沉默複合體(RISC)結合而進行RNA干擾,切割目標mRNA或抑制其轉譯以達成基因靜默的效果[15]

Drosha切割pri-miRNA時會與兩個RNA結合蛋白DGCR8共同組成稱為微加工复合体英语Microprocessor complex蛋白三聚體[16][17][18][19],DGCR8在模式生物黑腹果蠅秀麗隱桿線蟲中稱為Pasha,即「Drosha的夥伴蛋白」(partner of Drosha)之簡稱[20],Drosha需在與DGCR8結合的情況下才能進行切割[21]。除必要的Drosha與DGCR8外,微加工复合体還可能包含EWSR1英语EWSR1异质核糖核蛋白英语Heterogeneous ribonucleoprotein particle、FUS與DEAD-BoxRNA解旋酶p68英语DDX5p72英语DDX17)等其他蛋白以幫助切割pri-miRNA[22][23],有些種類的pri-miRNA只有在特定輔助蛋白存在時才能被Drosha切割[24]

Drosha大多位於細胞核中,但也有些Drosha不含核定位序列(NLS)而位於細胞質中,稱為c-Drosha,可能以其他機制調控基因表現[25][26]。另外Drosha與Dicer也參與DNA修補[27]

少數miRNA以非典型的方式生成,不需經Drosha切割,此類miRNA稱為Mirtron英语Mirtron,編碼序列位於其他基因的內含子中,可隨該基因的mRNA轉錄後進行剪接時被切割形成pre-miRNA,因此不需依賴Drosha[28];此外,還有些miRNA(simtron)前驅物的切割仰賴Drosha,但不需DGCR8、XPO5與Dicer[29]

臨床意義

Drosha等參與miRNA生成的蛋白表現量與某些癌症相關[12],例如某些種類的乳癌病患的Drosha與Dicer的表現量下降[30]癌症基因組圖譜中也顯示數種乳癌、大腸癌食道癌病患細胞質中的Drosha(即c-Drosha)表現量增加[25]

參考文獻

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外部連結