A conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay
A conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay
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DOI：
10.1038/sj.emboj.7601588
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发表时间：
2007-03-21
期刊：
影响因子：
11.4
通讯作者：
Izaurralde, Elisa
中科院分区：
文献类型：
--
作者：
Behm-Ansmant, Isabelle;Gatfield, David;Izaurralde, Elisa
无义介导的mRNA衰变（NMD）途径降解带有早翻译终止密码子（ptc）的mRNA。ptc和天然终止密码子的区别机制尚不清楚。我们发现，相对于聚(A)尾部（以及PABPC1）的停止位置是果蝇PTC定义的关键决定因素。事实上，PTC下游的PABPC1系缚消除了NMD。相反，当30 UTR的长度增加时，自然停止触发NMD。然而，许多具有异常长的30 UTR的内源性转录本逃脱了NMD，这表明30 UTR长度的增加与抑制NMD的特征的获得共同进化。我们提供证据证明存在30个给予NMD免疫的utr。我们还表明，PABPC1结合足以识别PTC，无论切割或聚腺苷化。PABPC1在NMD中的作用必须超越为PTC定义提供位置信息的作用，因为它的耗尽在不影响翻译效率的条件下抑制了NMD。这些发现揭示了PABPC1在mRNA监视中的保守作用。
The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs with premature translation termination codons (PTCs). The mechanisms by which PTCs and natural stop codons are discriminated remain unclear. We show that the position of stops relative to the poly( A) tail ( and thus of PABPC1) is a critical determinant for PTC definition in Drosophila melanogaster. Indeed, tethering of PABPC1 downstream of a PTC abolishes NMD. Conversely, natural stops trigger NMD when the length of the 30 UTR is increased. However, many endogenous transcripts with exceptionally long 30 UTRs escape NMD, suggesting that the increase in 30 UTR length has co-evolved with the acquisition of features that suppress NMD. We provide evidence for the existence of 30 UTRs conferring immunity to NMD. We also show that PABPC1 binding is sufficient for PTC recognition, regardless of cleavage or polyadenylation. The role of PABPC1 in NMD must go beyond that of providing positional information for PTC definition, because its depletion suppresses NMD under conditions in which translation efficiency is not affected. These findings reveal a conserved role for PABPC1 in mRNA surveillance.