Recognition of the spliceosomal branch site RNA helix on the basis of surface and electrostatic features.
Recognition of the spliceosomal branch site RNA helix on the basis of surface and electrostatic features.
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DOI：
10.1093/nar/gki249
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发表时间：
2005
影响因子：
14.9
通讯作者：
Fenley MO
中科院分区：
文献类型：
--
作者：
Xu D;Greenbaum NL;Fenley MO
我们研究了剪接体催化核心的一个重要区域--真核前体信使(Pre-m)RNA剪接装置的静电和表面特征。两个剪接反应中第一个的亲核性是内含子内特定腺苷核糖的2‘-羟基(OH)。在剪接体催化核心的组装过程中，这种腺苷通过与U2小核(Sn)RNA的一小段区域配对来定位，形成前mRNA分支位置的螺旋。剪接体前mRNA分支位点的溶液结构[Newby，M.I.和Greenbaum，N.L.(2002)Natural Struct.Biol.，9958-965]表明，U2SnRNA片段中与内含子配对的系统发育保守的伪尿苷(ψ)残基与其未修饰的对应物相比，诱导了明显不同的结构。为了更详细地了解影响剪接体分支位点螺旋识别和亲核试剂激活的因素，我们计算了ψ修饰和未修饰的分支位点双链的表面积和静电势。修饰和未修饰双链的总可及面积或总极性基团/非极性基团的比率无显著差异。然而，在ψ修饰的结构中，腺嘌呤碱基的非极性区域有更大的暴露，而2‘-OH的暴露更少。用混合边界元和有限差分非线性Poisson-Boltzmann方法计算静电势[Boschisch，A.H.和Fenley，M.O.(2004)J.Comput]。化学，25,935-955]揭示了在腺苷分支部位的2‘-OH周围的主要沟槽中有一个异常负的电势区域。这些表面和静电特征可能有助于剪接反应的其他成分对前mRNA分支位点区域的整体识别。
We have investigated electrostatic and surface features of an essential region of the catalytic core of the spliceosome, the eukaryotic precursor messenger (pre-m)RNA splicing apparatus. The nucleophile for the first of two splicing reactions is the 2′-hydroxyl (OH) of the ribose of a specific adenosine within the intron. During assembly of the spliceosome's catalytic core, this adenosine is positioned by pairing with a short region of the U2 small nuclear (sn)RNA to form the pre-mRNA branch site helix. The solution structure of the spliceosomal pre-mRNA branch site [Newby,M.I. and Greenbaum,N.L. (2002) Nature Struct. Biol., 9, 958–965] showed that a phylogenetically conserved pseudouridine (ψ) residue in the segment of U2 snRNA that pairs with the intron induces a markedly different structure compared with that of its unmodified counterpart. In order to achieve a more detailed understanding of the factors that contribute to recognition of the spliceosome's branch site helix and activation of the nucleophile for the first step of pre-mRNA splicing, we have calculated surface areas and electrostatic potentials of ψ-modified and unmodified branch site duplexes. There was no significant difference between the total accessible area or ratio of total polar:nonpolar groups between modified and unmodified duplexes. However, there was substantially greater exposure of nonpolar area of the adenine base, and less exposure of the 2′-OH, in the ψ-modified structure. Electrostatic potentials computed using a hybrid boundary element and finite difference nonlinear Poisson–Boltzmann approach [Boschitsch, A.H. and Fenley, M.O. (2004) J. Comput. Chem., 25, 935–955] revealed a region of exceptionally negative potential in the major groove surrounding the 2′-OH of the branch site adenosine. These surface and electrostatic features may contribute to the overall recognition of the pre-mRNA branch site region by other components of the splicing reaction.
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影响因子：
14.9
作者：
Leontis, NB;Stombaugh, J;Westhof, E
通讯作者：
Westhof, E
影响因子：
5.6
作者：
LEE, B;RICHARDS, FM
通讯作者：
RICHARDS, FM
影响因子：
14.9
作者：
LAVERY, R;PULLMAN, B
通讯作者：
PULLMAN, B
影响因子：
2.9
作者：
NICHOLLS, A;SHARP, KA;HONIG, B
通讯作者：
HONIG, B
DOI：
10.1038/nsb873
发表时间：
2002-12-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Newby, MI;Greenbaum, NL
通讯作者：
Greenbaum, NL