Recognition of Adenosine Residues by the Active Site of Poly(A)-specific Ribonuclease
Recognition of Adenosine Residues by the Active Site of Poly(A)-specific Ribonuclease
复制标题
DOI：
10.1074/jbc.m109.043893
复制
发表时间：
2010-01-01
影响因子：
4.8
通讯作者：
Virtanen, Anders
中科院分区：
文献类型：
--
作者：
Henriksson, Niklas;Nilsson, Per;Virtanen, Anders
Poly(A)-specific核糖核酸酶（PARN）是一种具有高特异性降解Poly(A)的哺乳动物3'-外核糖核酸酶。为了揭示聚(A)被PARN活性位点识别的机制，我们使用大量三核苷酸底物进行了动力学分析。我们的分析表明，PARN在其活性位点具有腺苷识别的特异性，并且围绕可剪切键的核苷酸对腺苷识别至关重要。我们提出两个结合袋，它们与可剪切键周围的核苷酸相互作用，在提供PARN活性位点识别腺苷残基的特异性方面发挥关键作用。此外，我们表明，除了聚(A)， PARN也相当有效地降解聚(U)，效率比聚(A)低10倍。PARN的聚(U)降解特性可能具有生物学意义，因为寡核苷酸(U)尾部最近被提出在RNA稳定和不稳定中发挥作用。
Poly(A)-specific ribonuclease (PARN) is a mammalian 3'-exoribonuclease that degrades poly(A) with high specificity. To reveal mechanisms by which poly(A) is recognized by the active site of PARN, we have performed a kinetic analysis using a large repertoire of trinucleotide substrates. Our analysis demonstrated that PARN harbors specificity for adenosine recognition in its active site and that the nucleotides surrounding the scissile bond are critical for adenosine recognition. We propose that two binding pockets, which interact with the nucleotides surrounding the scissile bond, play a pivotal role in providing specificity for the recognition of adenosine residues by the active site of PARN. In addition, we show that PARN, besides poly(A), also quite efficiently degrades poly(U), similar to 10-fold less efficiently than poly(A). The poly(U)-degrading property of PARN could be of biological significance as oligo(U) tails recently have been proposed to play a role in RNA stabilization and destabilization.