Nonsense-mediated mRNA decay: a 'nonsense' pathway makes sense in stem cell biology.
Nonsense-mediated mRNA decay: a 'nonsense' pathway makes sense in stem cell biology.
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无义介导的 mRNA 衰减：“无义”途径在干细胞生物学中有意义
DOI：
10.1093/nar/gkx1272
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发表时间：
2018-02-16
影响因子：
14.9
通讯作者：
Li T
中科院分区：
文献类型：
--
作者：
Han X;Wei Y;Wang H;Wang F;Ju Z;Li T
无义介导的mRNA衰变（NMD）是真核生物中高度保守的基因表达转录后调控机制。最初，NMD被鉴定为降解具有提前终止密码子的“异常”mRNA种类的RNA监视机制。最近的研究表明，NMD调节在细胞功能中发挥重要作用的天然基因转录本的稳定性。虽然NMD机制在降解其RNA靶标中的组分和作用模式已经用生物化学和结构方法进行了广泛的研究，但NMD的生物学作用仍有待确定。干细胞是一种罕见的细胞群，在组织内环境稳定中发挥重要作用，在再生医学中具有巨大的前景。干细胞自我更新以维持细胞身份并分化成具有维持组织完整性的专门功能的体细胞谱系。转录调控和表观遗传调节已广泛涉及干细胞生物学。然而，转录后调控机制，如NMD，在干细胞调控在很大程度上是未知的。本文就NMD因子在胚胎干细胞和组织特异性干细胞中的生物学作用作一综述。此外，我们还讨论了NMD调节干细胞命运的可能机制。
Nonsense-mediated mRNA decay (NMD) is a highly conserved post-transcriptional regulatory mechanism of gene expression in eukaryotes. Originally, NMD was identified as an RNA surveillance machinery in degrading ‘aberrant’ mRNA species with premature termination codons. Recent studies indicate that NMD regulates the stability of natural gene transcripts that play significant roles in cell functions. Although components and action modes of the NMD machinery in degrading its RNA targets have been extensively studied with biochemical and structural approaches, the biological roles of NMD remain to be defined. Stem cells are rare cell populations, which play essential roles in tissue homeostasis and hold great promises in regenerative medicine. Stem cells self-renew to maintain the cellular identity and differentiate into somatic lineages with specialized functions to sustain tissue integrity. Transcriptional regulations and epigenetic modulations have been extensively implicated in stem cell biology. However, post-transcriptional regulatory mechanisms, such as NMD, in stem cell regulation are largely unknown. In this paper, we summarize the recent findings on biological roles of NMD factors in embryonic and tissue-specific stem cells. Furthermore, we discuss the possible mechanisms of NMD in regulating stem cell fates.
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