無終止密碼子媒介式分解

(重定向自无终止降解

無終止密碼子媒介式分解(Non-stop decay,簡稱NSD)為真核生物細胞移除不含終止密碼子的異常mRNA之機制。核糖體轉譯不具終止密碼子的mRNA(可能因突變多腺苷酸化位點異常、在開放閱讀框中間被切割等原因產生[2])後,會繼續轉譯mRNA的3'非轉譯區(3'UTR),最後停滯於其末端的多聚腺苷酸尾而無法正常脫離,核糖體轉譯多聚腺苷酸尾時會合成帶正電的多離氨酸序列,也會使多肽鏈與帶負電的rRNA互動而停滯於核糖體的多肽通道中[2]

酵母菌中的兩種無終止密碼子媒介式分解(NSD)途徑示意圖[1]

核糖體停滯發生後,細胞會啟動無終止密碼子媒介式分解途徑(NSD),Ski7英语Ski complex蛋白(酵母菌)或Hbs1及Dom34蛋白[註 1](哺乳類等)會前來與停滯的核糖體結合,將其自mRNA上釋出,再由外切體複合物將mRNA降解移除[2][3][4];另外酵母菌還有另一不使用ski7蛋白的NSD途徑,即核糖體轉譯造成多聚腺苷酸結合蛋白(PABP)自多聚腺苷酸尾脫落,進而造成5′端帽也跟著脫落、mRNA被外切酶xrn1英语XRN1 (gene)降解移除[5]

註腳 编辑

  1. ^ 這兩種蛋白也被用於轉譯停滯分解途徑(NGD)中[2]

參見 编辑

參考文獻 编辑

  1. ^ Garneau NL, Wilusz J, Wilusz CJ. The highways and byways of mRNA decay. Nature Reviews. Molecular Cell Biology. February 2007, 8 (2): 113–26. PMID 17245413. S2CID 14107577. doi:10.1038/nrm2104. 
  2. ^ 2.0 2.1 2.2 2.3 Karamyshev AL, Karamysheva ZN. Lost in Translation: Ribosome-Associated mRNA and Protein Quality Controls.. Front Genet. 2018, 9: 431. PMC 6180196 . PMID 30337940. doi:10.3389/fgene.2018.00431. 
  3. ^ Vasudevan; Peltz, SW; Wilusz, CJ; et al. Non-stop decay--a new mRNA surveillance pathway. BioEssays. 2002, 24 (9): 785–8. PMID 12210514. doi:10.1002/bies.10153. 
  4. ^ Venkataraman, K; Guja, KE; Garcia-Diaz, M; Karzai, AW. Non-stop mRNA decay: a special attribute of trans-translation mediated ribosome rescue.. Frontiers in Microbiology. 2014, 5: 93. PMC 3949413 . PMID 24653719. doi:10.3389/fmicb.2014.00093 . 
  5. ^ Frischmeyer PA, van Hoof A, O'Donnell K, Guerrerio AL, Parker R, Dietz HC. An mRNA surveillance mechanism that eliminates transcripts lacking termination codons. Science. March 2002, 295 (5563): 2258–61. Bibcode:2002Sci...295.2258F. PMID 11910109. S2CID 40843312. doi:10.1126/science.1067338.