The bicoid mRNA localization factor Exuperantia is an RNA-binding pseudonuclease

The bicoid mRNA localization factor Exuperantia is an RNA-binding pseudonuclease
复制标题

DOI:
10.1038/nsmb.3254
复制
发表时间:
2016-08-01
影响因子:
16.8
通讯作者:
Bono,Fulvia
Bono,Fulvia
中科院分区:
生物学1区
文献类型:
--
作者:
Lazzaretti,Daniela;Veith,Katharina;Bono,Fulvia

文献摘要

被引文献

相似文献

果蝇卵母细胞前极bicoid(bcd) mRNA定位介导的前向模式。Exuperantia (Exu)是一种推测的与bcd相关的外切酶(EXO),是bcd定位所必需的。我们展示了Exu的晶体结构,它揭示了一个二聚体组装,每个单体由一个3 ' -5 ' exo样结构域和一个无菌α基序(SAM)样结构域组成。催化位点是简并的和无活性的。相反,exo样结构域介导二聚化和RNA结合。我们发现Exu在体外直接结合RNA, sam样结构域是RNA结合活性所必需的,并且Exu以高亲和力结合存在于bcd3 '非翻译区的结构元件。通过结构导向诱变,我们发现Exu二聚化对定位至关重要。我们的数据表明,Exu是一种非规范RNA结合蛋白,具有exo - sam样结构域结构,与靶RNA作为同二聚体相互作用。
Anterior patterning inDrosophilais mediated by the localization ofbicoid(bcd) mRNA at the anterior pole of the oocyte. Exuperantia (Exu) is a putative exonuclease (EXO) associated withbcdand required for its localization. We present the crystal structure of Exu, which reveals a dimeric assembly with each monomer consisting of a 3′-5′ EXO-like domain and a sterile alpha motif (SAM)-like domain. The catalytic site is degenerate and inactive. Instead, the EXO-like domain mediates dimerization and RNA binding. We show that Exu binds RNA directlyin vitro, that the SAM-like domain is required for RNA binding activity and that Exu binds a structured element present in thebcd3′ untranslated region with high affinity. Through structure-guided mutagenesis, we show that Exu dimerization is essential forbcdlocalization. Our data demonstrate that Exu is a noncanonical RNA-binding protein with EXO-SAM-like domain architecture that interacts with its target RNA as a homodimer.