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无意义介导的 mRNA 降解(NMD)在动物胚胎发生中的作用:死亡还是不死亡,这是个问题。

Nonsense-mediated mRNA decay (NMD) in animal embryogenesis: to die or not to die, that is the question.

机构信息

Department of Biochemistry and Biophysics and the Center for RNA Biology, School of Medicine and Dentistry, 601 Elmwood Avenue, Box 712, University of Rochester, Rochester, NY 14642, USA.

出版信息

Curr Opin Genet Dev. 2011 Aug;21(4):422-30. doi: 10.1016/j.gde.2011.03.008.

DOI:10.1016/j.gde.2011.03.008
PMID:21550797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3150509/
Abstract

Nonsense-mediated mRNA decay (NMD) is a well-studied cellular quality-control pathway. It decreases the half-lives of eukaryotic mRNAs that aberrantly contain premature termination codons and additionally regulates an estimated 10-20% of normal transcripts. NMD factors play crucial roles during embryogenesis in many animals. Here, we review data indicating that NMD factors are required for proper embryogenesis by discussing the abnormal developmental phenotypes that result when the abundance of individual NMD factors is either downregulated or completely eliminated. We conclude that while NMD per se affects the embryogenesis of all animals, it is required to avoid embryonic lethality in only some animals. The critical roles of many NMD factors in other metabolic pathways undoubtedly also contribute to embryonic development if not viability.

摘要

无意义介导的 mRNA 降解(NMD)是一种研究得很好的细胞质量控制途径。它降低了含有过早终止密码子的真核 mRNA 的半衰期,并且还调节了大约 10-20%的正常转录本。NMD 因子在许多动物的胚胎发生中起着至关重要的作用。在这里,我们通过讨论当单个 NMD 因子的丰度下调或完全消除时导致的异常发育表型,回顾表明 NMD 因子是胚胎发生所必需的的数据。我们的结论是,虽然 NMD 本身会影响所有动物的胚胎发生,但它只在某些动物中是避免胚胎致死所必需的。如果不是胚胎存活,许多 NMD 因子在其他代谢途径中的关键作用无疑也会促进胚胎发育。

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本文引用的文献

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Molecular mechanisms for the RNA-dependent ATPase activity of Upf1 and its regulation by Upf2.Upf1 的 RNA 依赖性 ATP 酶活性及其被 Upf2 调控的分子机制。
Mol Cell. 2011 Mar 18;41(6):693-703. doi: 10.1016/j.molcel.2011.02.010.
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Drosophila Upf1 and Upf2 loss of function inhibits cell growth and causes animal death in a Upf3-independent manner.果蝇 Upf1 和 Upf2 功能丧失会抑制细胞生长,并以 Upf3 不依赖的方式导致动物死亡。
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Dhx34 and Nbas function in the NMD pathway and are required for embryonic development in zebrafish.Dhx34 和 Nbas 在 NMD 途径中发挥作用,并且是斑马鱼胚胎发育所必需的。
Nucleic Acids Res. 2011 May;39(9):3686-94. doi: 10.1093/nar/gkq1319. Epub 2011 Jan 11.
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Upf1 ATPase-dependent mRNP disassembly is required for completion of nonsense- mediated mRNA decay.Upf1 ATPase 依赖性 mRNP 解体是完成无意义介导的 mRNA 降解所必需的。
Cell. 2010 Dec 10;143(6):938-50. doi: 10.1016/j.cell.2010.11.043.
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Cutting the nonsense: the degradation of PTC-containing mRNAs.摒弃废话:含 PTC 的 mRNAs 的降解。
Biochem Soc Trans. 2010 Dec;38(6):1615-20. doi: 10.1042/BST0381615.
6
Nonsense-mediated mRNA decay and development: shoot the messenger to survive?无义介导的 mRNA 衰变与发育:枪毙信使以求生?
Biochem Soc Trans. 2010 Dec;38(6):1500-5. doi: 10.1042/BST0381500.
7
Coordinate regulation of histone mRNA metabolism and DNA replication: cyclin A/cdk1 is involved in inactivation of histone mRNA metabolism and DNA replication at the end of S phase.组蛋白 mRNA 代谢和 DNA 复制的协调调控:细胞周期蛋白 A/CDK1 参与 S 期结束时组蛋白 mRNA 代谢和 DNA 复制的失活。
Cell Cycle. 2010 Oct 1;9(19):3857-63. doi: 10.4161/cc.9.19.13300. Epub 2010 Oct 9.
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SMG6 interacts with the exon junction complex via two conserved EJC-binding motifs (EBMs) required for nonsense-mediated mRNA decay.SMG6 通过两个保守的外显子结合基序(EBMs)与exon junction complex 相互作用,这两个基序对于无意义介导的 mRNA 降解是必需的。
Genes Dev. 2010 Nov 1;24(21):2440-50. doi: 10.1101/gad.604610. Epub 2010 Oct 7.
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The exon junction complex differentially marks spliced junctions.外显子连接复合物差异标记拼接接头。
Nat Struct Mol Biol. 2010 Oct;17(10):1269-71. doi: 10.1038/nsmb.1890. Epub 2010 Sep 5.
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NMD: RNA biology meets human genetic medicine.NMD:RNA 生物学与人类遗传医学的交汇。
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