Structure-function analysis of the RNA helicase maleless.
Structure-function analysis of the RNA helicase maleless.
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DOI：
10.1093/nar/gkm1108
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发表时间：
2008-02
影响因子：
14.9
通讯作者：
Becker PB
中科院分区：
文献类型：
--
作者：
Izzo A;Regnard C;Morales V;Kremmer E;Becker PB
果蝇无雄性RNA解旋酶（MLE）功能的丧失导致雄性特异性致死，这是由于X染色体剂量补偿的失败。MLE可能参与将非编码roX RNA整合到剂量补偿复合物（DCC）中，这是将复合物忠实靶向X染色体的必要但知之甚少的要求。序列比较预测了几个RNA结合结构域的MLE，但他们的属性还没有得到实验验证。我们评估了这些保守基序的RNA结合特性及其对RNA刺激的ATP酶活性、解旋酶活性以及MLE靶向细胞核和X染色体区域的贡献。我们发现，RB 2是占主导地位的，有条件的RNA结合模块，这是必不可少的ATP酶和解旋酶活性，而N-末端RB 1基序不结合RNA，但参与靶向MLE的X染色体。含有富含甘氨酸的七肽重复的C-末端结构域增加了解旋酶活性不需要的潜在二聚化和RNA结合表面。
Loss of function of the RNA helicase maleless (MLE) in Drosophila melanogaster leads to male-specific lethality due to a failure of X chromosome dosage compensation. MLE is presumably involved in incorporating the non-coding roX RNA into the dosage compensation complex (DCC), which is an essential but poorly understood requirement for faithful targeting of the complex to the X chromosome. Sequence comparison predicts several RNA-binding domains in MLE but their properties have not been experimentally verified. We evaluated the RNA-binding characteristics of these conserved motifs and their contributions to RNA-stimulated ATPase activity, to helicase activity, as well as to the targeting of MLE to the nucleus and to the X chromosome territory. We find that RB2 is the dominant, conditional RNA-binding module, which is indispensable for ATPase and helicase activity whereas the N-terminal RB1 motif does not bind RNA, but is involved in targeting MLE to the X chromosome. The C-terminal domain containing a glycine-rich heptad repeat adds potential dimerization and RNA-binding surfaces which are not required for helicase activity.
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