Rules that govern UPF1 binding to mRNA 3′ UTRs
Rules that govern UPF1 binding to mRNA 3′ UTRs
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DOI：
10.1073/pnas.1219908110
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发表时间：
2013-02-26
影响因子：
11.1
通讯作者：
Maquat, Lynne E.
中科院分区：
文献类型：
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作者：
Kurosaki, Tatsuaki;Maquat, Lynne E.
无义介导的mRNA衰变（NMD），降解含有提前终止密码子（PTC）的转录本，依赖于解旋酶上移码1（UPF 1）。然而，不是NMD靶标的mRNA也结合UPF 1。UPF 1与mRNA结合的时间、位置和功能尚不清楚。我们提供的证据表明：（i）多个UPF 1分子在含PTC的mRNA的3 '非翻译区（3' UTR）上积累，并且如果mRNA是NMD靶标，则每单位3' UTR长度积累的程度更大;（ii）UPF 1结合开始于PTC下游>= 35 nt;（iii）相对于不含PTC的对应物，UPF 1与含PTC的mRNA的3' UTR的结合增强取决于翻译;和（iv）3' UTR外显子-连接复合物（EJC）的存在进一步增强UPF 1结合和/或亲和力。我们的数据表明，无论3' UTR是否包含EJC，NMD都涉及UPF 1沿着3' UTR结合。这种结合解释了没有3' UTR EJC但具有异常长的3' UTR的mRNA如何成为NMD靶标，尽管不如含有3' UTR EJC的对应物有效。
Nonsense-mediated mRNA decay (NMD), which degrades transcripts harboring a premature termination codon (PTC), depends on the helicase up-frameshift 1 (UPF1). However, mRNAs that are not NMD targets also bind UPF1. What governs the timing, position, and function of UPF1 binding to mRNAs remains unclear. We provide evidence that (i) multiple UPF1 molecules accumulate on the 3'-untranslated region (3' UTR) of PTC-containing mRNAs and to an extent that is greater per unit 3' UTR length if the mRNA is an NMD target; (ii) UPF1 binding begins >= 35 nt downstream of the PTC; (iii) enhanced UPF1 binding to the 3' UTR of PTC-containing mRNA relative to its PTC-free counterpart depends on translation; and (iv) the presence of a 3' UTR exon-junction complex (EJC) further enhances UPF1 binding and/or affinity. Our data suggest that NMD involves UPF1 binding along a 3' UTR whether the 3' UTR contains an EJC. This binding explains how mRNAs without a 3' UTR EJC but with an abnormally long 3' UTR can be NMD targets, albeit not as efficiently as their counterparts that contain a 3' UTR EJC.