An RNA decay factor wears a new coat: UPF3B modulates translation termination.
An RNA decay factor wears a new coat: UPF3B modulates translation termination.
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DOI：
10.12688/f1000research.12704.1
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Wilkinson M
中科院分区：
文献类型：
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作者：
Gao Z;Wilkinson M
无义介导的RNA衰变（NMD）是一种高度保守和选择性的RNA周转途径，一直受到严格的审查。NMD鉴定并降解正常RNA的子集，以及含有提前终止密码子的异常mRNA。UPF 3B是这条通路中的一个核心因子，它是一个衔接蛋白，作为NMD放大器和NMD分支特异性因子。UPF 3B由一个X连锁基因编码，该基因突变时会导致智力残疾，并与精神分裂症和自闭症等神经发育障碍有关。Neu-Yilik等人现在报道了UPF 3B的一个新功能：它调节翻译终止。使用完全重建的体外翻译系统，他们发现UPF 3B在翻译终止中有两个作用。首先，UPF 3B在模拟过早翻译终止的条件下延迟翻译终止。这可以通过允许更多的时间形成RNA衰变刺激复合物来驱动更有效的RNA衰变。其次，UPF 3B促进缺乏新生肽的终止后核糖体复合物的解离。这意味着UPF 3B可以促进核糖体再循环。重要的是，作者发现UPF 3B直接与RNA和识别终止密码子的因子-真核释放因子（eRFs）相互作用，这表明UPF 3B是翻译终止的直接调节因子。相比之下，NMD因子先前被认为在翻译终止中具有中心调节作用-RNA解旋酶UPF 1-被发现与eRFs间接相互作用，并且似乎仅在翻译后终止事件中起作用，例如RNA衰变，至少在体外。RNA衰变促进因子UFP 3B调节翻译终止的发现具有许多意义。例如，UPF 3B影响中枢神经系统发育和功能的能力可能不仅是通过其降解特定RNA的能力，而且还通过其对翻译终止和后续事件（如核糖体再循环）的影响。
Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA turnover pathway that has been subject to intense scrutiny. NMD identifies and degrades subsets of normal RNAs, as well as abnormal mRNAs containing premature termination codons. A core factor in this pathway—UPF3B—is an adaptor protein that serves as an NMD amplifier and an NMD branch-specific factor. UPF3B is encoded by an X-linked gene that when mutated causes intellectual disability and is associated with neurodevelopmental disorders, including schizophrenia and autism. Neu-Yilik et al. now report a new function for UPF3B: it modulates translation termination. Using a fully reconstituted in vitro translation system, they find that UPF3B has two roles in translation termination. First, UPF3B delays translation termination under conditions that mimic premature translation termination. This could drive more efficient RNA decay by allowing more time for the formation of RNA decay-stimulating complexes. Second, UPF3B promotes the dissociation of post-termination ribosomal complexes that lack nascent peptide. This implies that UPF3B could promote ribosome recycling. Importantly, the authors found that UPF3B directly interacts with both RNA and the factors that recognize stop codons—eukaryotic release factors (eRFs)—suggesting that UPF3B serves as a direct regulator of translation termination. In contrast, a NMD factor previously thought to have a central regulatory role in translation termination—the RNA helicase UPF1—was found to indirectly interact with eRFs and appears to act exclusively in post-translation termination events, such as RNA decay, at least in vitro. The finding that an RNA decay-promoting factor, UFP3B, modulates translation termination has many implications. For example, the ability of UPF3B to influence the development and function of the central nervous system may be not only through its ability to degrade specific RNAs but also through its impact on translation termination and subsequent events, such as ribosome recycling.