ZBP1 recognition of β-actin zipcode induces RNA looping
ZBP1 recognition of β-actin zipcode induces RNA looping
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DOI：
10.1101/gad.1862910
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发表时间：
2010-01-15
影响因子：
10.5
通讯作者：
Singer, Robert H.
中科院分区：
文献类型：
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作者：
Chao, Jeffrey A.;Patskovsky, Yury;Singer, Robert H.
ZBP1 （zipcode binding protein 1）最初被发现是β -肌动蛋白mRNA 39非翻译区（UTR）“zipcode”的反式作用因子，对其定位和翻译调控很重要。随后，ZBP1被发现是RNA代谢的多功能调节剂，控制许多mrna的定位、稳定性和翻译等方面。为了揭示ZBP1如何识别其RNA靶标，我们对ZBP1与β -肌动蛋白邮编之间的相互作用进行了生化表征。ZBP1的第三和第四个KH （hnRNP K同源）结构域特异性识别位于邮政编码前28个核苷酸内的二部RNA元件。RNA序列之间的间距与我们通过x射线晶体学解决的ZBP1的人类同源物IMP1 KH34的结构一致。串联KH结构域排列成分子内反平行的假二聚体构象，典型rna结合面位于分子的两端。KH结构域的这种取向要求RNA主干必须经历类似180度的方向变化，以便两个KH结构域同时与RNA接触。ZBP1结合诱导的RNA环化提供了一种特异性识别机制，并可能通过重塑结合的转录物促进转录后调控复合物的组装。
ZBP1 (zipcode-binding protein 1) was originally discovered as a trans-acting factor for the "zipcode" in the 39 untranslated region (UTR) of the beta-actin mRNA that is important for its localization and translational regulation. Subsequently, ZBP1 has been found to be a multifunctional regulator of RNA metabolism that controls aspects of localization, stability, and translation for many mRNAs. To reveal how ZBP1 recognizes its RNA targets, we biochemically characterized the interaction between ZBP1 and the beta-actin zipcode. The third and fourth KH (hnRNP K homology) domains of ZBP1 specifically recognize a bipartite RNA element located within the first 28 nucleotides of the zipcode. The spacing between the RNA sequences is consistent with the structure of IMP1 KH34, the human ortholog of ZBP1, that we solved by X-ray crystallography. The tandem KH domains are arranged in an intramolecular anti-parallel pseudodimer conformation with the canonical RNA-binding surfaces at opposite ends of the molecule. This orientation of the KH domains requires that the RNA backbone must undergo an similar to 180 degrees change in direction in order for both KH domains to contact the RNA simultaneously. The RNA looping induced by ZBP1 binding provides a mechanism for specific recognition and may facilitate the assembly of post-transcriptional regulatory complexes by remodeling the bound transcript.