核糖體停滯

核糖體停滯（Ribosomal pause, Ribosomal stall）是細胞中核糖體轉譯mRNA時發生停滯的現象，在原核生物與真核生物細胞中皆會發生。核糖體分析（英语：ribosome profiling）等實驗技術可用於找出mRNA中發生核糖體停滯的位點。 早在1980年代即有研究顯示核糖體轉譯mRNA不同區域的的速率不一致，當時認為轉譯較慢的位點是因含有罕見的密碼子，對應的tRNA在細胞中含量較少，因此與mRNA結合所需的時間較長。但近年核糖體分析的實驗結果顯示核糖體發生停滯的位點與其對應tRNA的含量不一定有關，意即有些核糖體停滯並非由罕見密碼子造成。除此之外造成核糖體停滯的原因還有多脯氨酸序列（polyproline）、tRNA未活化（未連接氨基酸）等，此類停滯為可逆，可由eIF5A（英语：EIF5A）（真核生物）或EFP（原核生物）蛋白解決，為細胞調控轉譯的機制之一，除控制蛋白質轉譯的產量，還可能與蛋白質摺疊有關（即在蛋白質的結構域轉譯結束時發生停滯，讓其有時間完成折疊），或者促使核糖體移碼發生。缺少eIF5A的真核細胞發生核糖體停滯的頻率會增加。 有時核糖體停滯為不可逆，原核生物與真核生物皆有將核糖體自mRNA釋出的機制。當真核細胞中mRNA上不具終止密碼子時，核糖體轉譯後會停滯於mRNA的末端，此時細胞會啟動無終止密碼子媒介式分解途徑（NSD）將核糖體釋出，並將該mRNA與轉譯的多肽產物降解；有時核糖體會遇到mRNA上較複雜的二級結構而停滯，細胞則可啟動轉譯停滯分解（no-go decay，NGD）途徑，亦可將核糖體釋出，並降解mRNA及多肽產物。細菌則可以转运-信使RNA（tmRNA）啟動反式轉譯來處理停滯的核糖體，部分細菌還有ArfA（英语：Alternative ribosome-rescue factor A）、ArfB（英语：Alternative ribosome-rescue factor B）等其他途徑。 分子与细胞生物学主题 Buskirk, Allen R.; Green, Rachel. Ribosome pausing, arrest and rescue in bacteria and eukaryotes. Philosophical Transactions of the Royal Society B: Biological Sciences. 2017, 372 (1716): 20160183. PMC 5311927 . PMID 28138069. doi:10.1098/rstb.2016.0183.  Li GW, Oh E, Weissman JS. The anti-Shine-Dalgarno sequence drives translational pausing and codon choice in bacteria. Nature. 2012, 484 (7395): 538–41 [2021-12-06]. Bibcode:2012Natur.484..538L. PMC 3338875 . PMID 22456704. doi:10.1038/nature10965. （原始内容存档于2021-12-06）.  Lopinski JD, Dinman JD, Bruenn JA. Kinetics of ribosomal pausing during programmed -1 translational frameshifting. Molecular and Cellular Biology. 2000, 20 (4): 1095–103. PMC 85227 . PMID 10648594. doi:10.1128/MCB.20.4.1095-1103.2000.  Brar GA, Yassour M, Friedman N, Regev A, Ingolia NT, Weissman JS. High-resolution view of the yeast meiotic program revealed by ribosome profiling. Science. 2012, 335 (6068): 552–7. Bibcode:2012Sci...335..552B. PMC 3414261 . PMID 22194413. doi:10.1126/science.1215110.  Kontos H, Napthine S, Brierley I. Ribosomal pausing at a frameshifter RNA pseudoknot is sensitive to reading phase but shows little correlation with frameshift efficiency. Molecular and Cellular Biology. 2001, 21 (24): 8657–70. PMC 100026 . PMID 11713298. doi:10.1128/MCB.21.24.8657-8670.2001.  Darnell AM, Subramaniam AR, O'Shea EK. Translational Control through Differential Ribosome Pausing during Amino Acid Limitation in Mammalian Cells. Molecular Cell. 2018, 71 (2): 229–243.e11. PMC 6516488 . PMID 30029003. doi:10.1016/j.molcel.2018.06.041.  Gawroński P, Jensen PE, Karpiński S, Leister D, Scharff LB. Pausing of Chloroplast Ribosomes Is Induced by Multiple Features and Is Linked to the Assembly of Photosynthetic Complexes. Plant Physiology. March 2018, 176 (3): 2557–2569. PMC 5841727 . PMID 29298822. doi:10.1104/pp.17.01564.  Buchan JR, Stansfield I. Halting a cellular production line: responses to ribosomal pausing during translation. Biology of the Cell. 2007, 99 (9): 475–87. PMID 17696878. doi:10.1042/BC20070037 .  Manjunath H, Zhang H, Rehfeld F, Han J, Chang TC, Mendell JT. Suppression of Ribosomal Pausing by eIF5A Is Necessary to Maintain the Fidelity of Start Codon Selection. Cell Reports. 2019, 29 (10): 3134–3146.e6. PMC 6917043 . PMID 31801078. doi:10.1016/j.celrep.2019.10.129.  Chan, KH; Petrychenko, V; Mueller, C; Maracci, C; Holtkamp, W; Wilson, DN; Fischer, N; Rodnina, MV. Mechanism of ribosome rescue by alternative ribosome-rescue factor B.. Nature Communications. 2020, 11 (1): 4106. PMC 7427801 . PMID 32796827. doi:10.1038/s41467-020-17853-7.