核糖核酸酶Z
核糖核酸酶Z(Ribonuclease Z、RNase Z、3′ tRNase,在不同生物中的名稱包括ElaC、ZiPD、RNase BN、TRZ1等)是一種參與tRNA生合成的核糖核酸酶,為內切酶,屬鋅依賴型金屬水解酶,編碼此蛋白的基因於2002年被發現[1][2]。
核糖核酸酶Z | |||||||
---|---|---|---|---|---|---|---|
![]() | |||||||
枯草桿菌的核糖核酸酶Z與tRNA結合的結構圖 | |||||||
| |||||||
識別碼 | |||||||
EC編號 | 3.1.26.11 | ||||||
CAS號 | 98148-84-6 | ||||||
數據庫 | |||||||
IntEnz | IntEnz瀏覽 | ||||||
BRENDA | BRENDA入口 | ||||||
ExPASy | NiceZyme瀏覽 | ||||||
KEGG | KEGG入口 | ||||||
MetaCyc | 代謝路徑 | ||||||
PRIAM | 概述 | ||||||
PDB | RCSB PDB PDBj PDBe PDBsum | ||||||
|
tRNA基因轉錄產生tRNA前驅物(pre-tRNA)後,其5′端會被核糖核酸酶P切割,3′端則被核糖核酸酶Z切割,隨後再由CCA tRNA核苷酸轉移酶在其3′端加上CCA三個鹼基,以生成成熟的tRNA[1][3][4]。核糖核酸酶Z切割位點下游位點的CC會抑制其切割活性,因此已被加上CCA的成熟tRNA不會再被其切割[2][註 1],此外tRNA前驅物5′端序列的長度也可能影響核糖核酸酶Z切割的活性[6][7]。
演化與功能
編輯三域生物皆有核糖核酸酶Z,已被定序的所有真核生物與古菌以及許多細菌皆有之,但變形菌門的細菌多不具此酵素。自然界中存在兩型的核糖核酸酶Z,較短的RNase ZS長280至360個氨基酸,見於三域生物[2];較長的RNase ZL長度約為前者兩倍,在演化上應是由前者經基因重複產生,只見於真核生物[2]。RNase ZS會以二聚體的形式切割tRNA,RNase ZL則是以單體的形式作用,且有研究顯示後者的切割活性比前者的高許多[6]。
脊椎動物與植物以外的真核生物(包括釀酒酵母、粟酒裂殖酵母、黑腹果蠅與秀麗隱桿線蟲等模式生物[2])經常只有RNase ZL[12];而同時具有RNase ZL和RNase ZS的生物中兩者在細胞中的位置可能不同[2],例如模式植物阿拉伯芥分別有兩個RNase ZS與RNase ZL,前者一個位於細胞質,一個位於葉綠體中,後者一個位於細胞核與粒線體,一個僅見於粒線體[13][14];釀酒酵母僅有RNase ZL,位於細胞核與粒線體中[8]。
人類的RNase ZL(ELAC2)基因有兩個起始密碼子,可轉錄產生兩種不同的mRNA,其中較長者包含一粒線體導向序列,會被送入粒線體中,負責切割粒線體基因組編碼的tRNA前驅物;較短者則會被送入細胞核中,切割細胞核編碼的tRNA前驅物,除產生成熟tRNA外,也參與tRNA片段(tRNA fragment)的生成,進而影響細胞內各種小RNA量的平衡[2][15][16]已知有ELAC2基因的突變與前列腺癌和心肌病變相關[6][8][17][18]。人類的RNase ZS(ELAC1)則位於細胞質中,其功能仍不甚清楚,有研究指其可能參與解決轉譯中核糖體停滯的反應途徑,停滯的核糖體上P位點的tRNA 3′端會被內切酶ANKZF1切割,將與其連結的多肽鏈和末端的CCA鹼基一起移除,造成tRNA最末端的核苷酸形成2′,3′-環磷酸(2′,3′-cyclic phosphate),ELAC1可能可切割此結構,使tRNA重新產生有活性的3′端,得以再被CCA tRNA核苷酸轉移酶作用接上CCA而重新利用[19][20]。
切割其他RNA
編輯除tRNA前驅物外,核糖核酸酶Z可能還可切割其他與tRNA前驅物結構相似的RNA。核糖核酸酶P與核糖核酸酶Z可切割MALAT1(一個長鏈非編碼RNA)的3′端,產生MALAT1相關胞漿小RNA(mascRNA)[21];另有一3′端和MALAT1高度相似的長鏈非編碼RNAMEN β RNA可能也可被核糖核酸酶P與核糖核酸酶Z切割,產生類似mascRNA的小RNA[22]。阿拉伯芥編碼tRNAGly的基因下游緊接著編碼snoR43家族的snoRNA基因,兩者會共同轉錄成一RNA前驅物,並被核糖核酸酶Z切割,以產生成熟的tRNA與snoRNA[23]。
參見
編輯註腳
編輯參考文獻
編輯- ^ 1.0 1.1 Schiffer S, Rösch S, Marchfelder A. Assigning a function to a conserved group of proteins: the tRNA 3'-processing enzymes. The EMBO Journal. 2002, 21 (11): 2769–77. PMC 126033 . PMID 12032089. doi:10.1093/emboj/21.11.2769.
- ^ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Redko Y, Li de la Sierra-Gallay I, Condon C. When all's zed and done: the structure and function of RNase Z in prokaryotes.. Nat Rev Microbiol. 2007, 5 (4): 278–86 [2022-06-21]. PMID 17363966. doi:10.1038/nrmicro1622. (原始內容存檔於2022-06-21).
- ^ Mayer M, Schiffer S, Marchfelder A. tRNA 3' processing in plants: nuclear and mitochondrial activities differ. Biochemistry. 2000, 39 (8): 2096–105. PMID 10684660. doi:10.1021/bi992253e.
- ^ Minagawa A, Takaku H, Takagi M, Nashimoto M. A novel endonucleolytic mechanism to generate the CCA 3' termini of tRNA molecules in Thermotoga maritima. The Journal of Biological Chemistry. 2004, 279 (15): 15688–97. PMID 14749326. doi:10.1074/jbc.M313951200 .
- ^ Minagawa A, Takaku H, Takagi M, Nashimoto M. A novel endonucleolytic mechanism to generate the CCA 3' termini of tRNA molecules in Thermotoga maritima.. J Biol Chem. 2004, 279 (15): 15688–97 [2022-06-21]. PMID 14749326. doi:10.1074/jbc.M313951200. (原始內容存檔於2022-06-21).
- ^ 6.0 6.1 6.2 6.3 Peng G, He Y, Wang M, Ashraf MF, Liu Z, Zhuang C; et al. The structural characteristics and the substrate recognition properties of RNase ZS1.. Plant Physiol Biochem. 2021, 158: 83–90 [2022-06-21]. PMID 33302124. doi:10.1016/j.plaphy.2020.12.001. (原始內容存檔於2022-06-21).
- ^ Pellegrini O, Nezzar J, Marchfelder A, Putzer H, Condon C. Endonucleolytic processing of CCA-less tRNA precursors by RNase Z in Bacillus subtilis.. EMBO J. 2003, 22 (17): 4534–43. PMC 202377 . PMID 12941704. doi:10.1093/emboj/cdg435.
- ^ 8.0 8.1 8.2 Ma M, Li de la Sierra-Gallay I, Lazar N, Pellegrini O, Durand D, Marchfelder A; et al. The crystal structure of Trz1, the long form RNase Z from yeast.. Nucleic Acids Res. 2017, 45 (10): 6209–6216. PMC 5449637 . PMID 28379452. doi:10.1093/nar/gkx216.
- ^ Kostelecky B, Pohl E, Vogel A, Schilling O, Meyer-Klaucke W. The crystal structure of the zinc phosphodiesterase from Escherichia coli provides insight into function and cooperativity of tRNase Z-family proteins.. J Bacteriol. 2006, 188 (4): 1607–14. PMC 1367222 . PMID 16452444. doi:10.1128/JB.188.4.1607-1614.2006.
- ^ Li de la Sierra-Gallay I, Pellegrini O, Condon C. Structural basis for substrate binding, cleavage and allostery in the tRNA maturase RNase Z.. Nature. 2005, 433 (7026): 657–61. PMID 15654328. doi:10.1038/nature03284.
- ^ Ishii R, Minagawa A, Takaku H, Takagi M, Nashimoto M, Yokoyama S. Crystal structure of the tRNA 3' processing endoribonuclease tRNase Z from Thermotoga maritima.. J Biol Chem. 2005, 280 (14): 14138–44. PMID 15701599. doi:10.1074/jbc.M500355200.
- ^ Wang Z, Zheng J, Zhang X, Peng J, Liu J, Huang Y. Identification and sequence analysis of metazoan tRNA 3'-end processing enzymes tRNase Zs.. PLoS One. 2012, 7 (9): e44264. PMC 3433465 . PMID 22962606. doi:10.1371/journal.pone.0044264.
- ^ Rossmanith W. Of P and Z: mitochondrial tRNA processing enzymes.. Biochim Biophys Acta. 2012, 1819 (9-10): 1017–26. PMC 3790967 . PMID 22137969. doi:10.1016/j.bbagrm.2011.11.003.
- ^ Canino G, Bocian E, Barbezier N, Echeverría M, Forner J, Binder S; et al. Arabidopsis encodes four tRNase Z enzymes.. Plant Physiol. 2009, 150 (3): 1494–502. PMC 2705019 . PMID 19411372. doi:10.1104/pp.109.137950.
- ^ Siira SJ, Rossetti G, Richman TR, Perks K, Ermer JA, Kuznetsova I; et al. Concerted regulation of mitochondrial and nuclear non-coding RNAs by a dual-targeted RNase Z.. EMBO Rep. 2018, 19 (10). PMC 6172459 . PMID 30126926. doi:10.15252/embr.201846198.
- ^ Rossmanith W. Localization of human RNase Z isoforms: dual nuclear/mitochondrial targeting of the ELAC2 gene product by alternative translation initiation.. PLoS One. 2011, 6 (4): e19152. PMC 3084753 . PMID 21559454. doi:10.1371/journal.pone.0019152.
- ^ Takaku H, Minagawa A, Takagi M, Nashimoto M. A candidate prostate cancer susceptibility gene encodes tRNA 3' processing endoribonuclease.. Nucleic Acids Res. 2003, 31 (9): 2272–8. PMC 154223 . PMID 12711671. doi:10.1093/nar/gkg337.
- ^ Haack TB, Kopajtich R, Freisinger P, Wieland T, Rorbach J, Nicholls TJ; et al. ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy.. Am J Hum Genet. 2013, 93 (2): 211–23. PMC 3738821 . PMID 23849775. doi:10.1016/j.ajhg.2013.06.006.
- ^ Yip MCJ, Savickas S, Gygi SP, Shao S. ELAC1 Repairs tRNAs Cleaved during Ribosome-Associated Quality Control.. Cell Rep. 2020, 30 (7): 2106–2114.e5. PMC 7067598 . PMID 32075755. doi:10.1016/j.celrep.2020.01.082.
- ^ Seki M, Komuro A, Takahashi M, Nashimoto M. Transcription from the proximal promoter of ELAC1, a gene for tRNA repair, is upregulated by interferons.. Biochem Biophys Res Commun. 2021, 585: 162–168. PMID 34808499. doi:10.1016/j.bbrc.2021.11.037.
- ^ Wilusz JE, Freier SM, Spector DL. 3' end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell. 2008, 135 (5): 919–32. PMC 2722846 . PMID 19041754. doi:10.1016/j.cell.2008.10.012.
- ^ Sunwoo H, Dinger ME, Wilusz JE, Amaral PP, Mattick JS, Spector DL. MEN epsilon/beta nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles. Genome Res. 2009, 19 (3): 347–359. PMC 2661813 . PMID 19106332. doi:10.1101/gr.087775.108.
- ^ Kruszka K, Barneche F, Guyot R, Ailhas J, Meneau I, Schiffer S; et al. Plant dicistronic tRNA-snoRNA genes: a new mode of expression of the small nucleolar RNAs processed by RNase Z.. EMBO J. 2003, 22 (3): 621–32. PMC 140725 . PMID 12554662. doi:10.1093/emboj/cdg040.