Features and factors that dictate if terminating ribosomes cause or counteract nonsense-mediated mRNA decay.
Features and factors that dictate if terminating ribosomes cause or counteract nonsense-mediated mRNA decay.
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DOI：
10.1016/j.jbc.2022.102592
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发表时间：
2022-11
影响因子：
4.8
通讯作者：
Singh, Guramrit
中科院分区：
文献类型：
--
作者：
Embree, Caleb M.;Abu-Alhasan, Rabab;Singh, Guramrit
无义介导的mRNA衰变（NMD）是真核生物中的质量控制途径，其连续监测mRNA转录物以确保不产生截短的多肽。许多编码全长多肽的正常mRNA的表达也受该途径调节。NMD的这种转录监测与翻译终止密切相关。当核糖体在正常的终止密码子处终止翻译时，NMD不被激活，并且mRNA可以经历重复的多轮翻译。另一方面，当翻译终止被认为是异常的，例如在提前终止密码子上的翻译终止，它导致一系列涉及NMD途径的知之甚少的事件，这使转录物不稳定。在这篇综述中，我们总结了我们目前的理解如何NMD机制接口的翻译终止因子启动NMD。我们还讨论了各种顺式作用序列上下文和反式作用因子，可以导致通读，核糖体重新启动，或核糖体移码终止密码子预测诱导NMD。这些替代的结果可以导致核糖体在这些终止密码子的下游翻译，因此转录物逃避NMD。NMD通过这些机制逃逸可能对人类健康产生广泛影响，从被病毒利用劫持宿主细胞系统到被利用作为治疗遗传疾病的潜在治疗可能性。
Nonsense-mediated mRNA decay (NMD) is a quality control pathway in eukaryotes that continuously monitors mRNA transcripts to ensure truncated polypeptides are not produced. The expression of many normal mRNAs that encode full-length polypeptides is also regulated by this pathway. Such transcript surveillance by NMD is intimately linked to translation termination. When a ribosome terminates translation at a normal termination codon, NMD is not activated, and mRNA can undergo repeated rounds of translation. On the other hand, when translation termination is deemed abnormal, such as that on a premature termination codon, it leads to a series of poorly understood events involving the NMD pathway, which destabilizes the transcript. In this review, we summarize our current understanding of how the NMD machinery interfaces with the translation termination factors to initiate NMD. We also discuss a variety of cis-acting sequence contexts and trans-acting factors that can cause readthrough, ribosome reinitiation, or ribosome frameshifting at stop codons predicted to induce NMD. These alternative outcomes can lead to the ribosome translating downstream of such stop codons and hence the transcript escaping NMD. NMD escape via these mechanisms can have wide-ranging implications on human health, from being exploited by viruses to hijack host cell systems to being harnessed as potential therapeutic possibilities to treat genetic diseases.
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DOI：
10.1261/rna.060541.116
发表时间：
2017-05
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Celik A;Baker R;He F;Jacobson A
通讯作者：
Jacobson A
影响因子：
14.9
作者：
Baradaran-Heravi A;Balgi AD;Hosseini-Farahabadi S;Choi K;Has C;Roberge M
通讯作者：
Roberge M
影响因子：
14.9
作者：
BROWN, CM;STOCKWELL, PA;TATE, WP
通讯作者：
TATE, WP
影响因子：
64.8
作者：
Amrani, N;Ganesan, R;Jacobson, A
通讯作者：
Jacobson, A
影响因子：
14.9
作者：
Beissel, Christian;Neumann, Bettina;Krebber, Heike
通讯作者：
Krebber, Heike