无终止密码子媒介式分解
无终止密码子媒介式分解(Non-stop decay,简称NSD)为真核生物细胞移除不含终止密码子的异常mRNA之机制。核糖体转译不具终止密码子的mRNA(可能因突变、多腺苷酸化位点异常、在开放阅读框中间被切割等原因产生[2])后,会继续转译mRNA的3'非转译区(3'UTR),最后停滞于其末端的多聚腺苷酸尾而无法正常脱离,核糖体转译多聚腺苷酸尾时会合成带正电的多离氨酸序列,也会使多肽链与带负电的rRNA互动而停滞于核糖体的多肽通道中[2]。
核糖体停滞发生后,细胞会启动无终止密码子媒介式分解途径(NSD),Ski7蛋白(酵母菌)或Hbs1及Dom34蛋白[注 1](哺乳类等)会前来与停滞的核糖体结合,将其自mRNA上释出,再由外切体复合物将mRNA降解移除[2][3][4];另外酵母菌还有另一不使用ski7蛋白的NSD途径,即核糖体转译造成多聚腺苷酸结合蛋白(PABP)自多聚腺苷酸尾脱落,进而造成5′端帽也跟著脱落、mRNA被外切酶xrn1降解移除[5]。
注脚
参见
- 转运-信使RNA(tmRNA):细菌的一种小RNA,可启动反式转译以移除不含终止密码子的mRNA
- 无义介导的mRNA降解(NMD)
- 转译停滞分解(NGD)
- mRNA检查
参考文献
- ^ 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.
- ^ 2.0 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.
- ^ 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.
- ^ 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 .
- ^ 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.