The importance of internal loops within RNA substrates of ADAR1
The importance of internal loops within RNA substrates of ADAR1
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DOI：
10.1006/jmbi.1999.2914
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发表时间：
1999-08-06
影响因子：
5.6
通讯作者：
Bass, BL
中科院分区：
文献类型：
--
作者：
Lehmann, KA;Bass, BL
作用于RNA的腺苷脱氨酶（ADAR）是将双链RNA（dsRNA）内的腺苷转化为肌苷的RNA编辑酶家族。尽管ADAR杂乱地对完全碱基配对的dsRNA进行脱氨基，但脱氨基仅限于含有错配、凸起和内环的dsRNA内的少数选定腺苷。作为了解RNA结构特征如何促进选择性的第一步，我们研究了阿达尔底物内内环的作用。我们观察到，dsRNA螺旋在相同的位点脱氨基，无论它是作为一个自由分子存在还是被内环侧翼。因此，内部环描绘了ADAR 1的螺旋末端。由于ADAR 1在比长RNA更少的腺苷处使短RNA脱氨基，环通过将长RNA分成更短的底物来减少RNA内的脱氨基数量。对于一系列序列相关的对称内环，较大的环（大于或等于6个核苷酸）充当螺旋末端，而较小的环（小于或等于4个核苷酸）则不充当螺旋末端。我们的工作提供了关于阿达尔底物的二级结构如何决定选择性的第一个信息，并提出了一个合理的方法来描绘最小底物的RNA脱氨基的ADAR在体内。(C)北京：科学出版社.
Adenosine deaminases that act on RNA (ADARs) are a family of RNA editing enzymes that convert adenosines to inosines within double-stranded RNA (dsRNA). Although ADARs deaminate perfectly base-paired dsRNA promiscuously, deamination is limited to a few, selected adenosines within dsRNA containing mismatches, bulges and internal loops. As a first step in understanding how RNA structural features promote selectivity, we investigated the role of internal loops within ADAR substrates. We observed that a dsRNA helix is deaminated at the same sites whether it exists as a free molecule or is flanked by internal loops. Thus, internal loops delineate helix ends for ADAR1. Since ADAR1 deaminates short RNAs at fewer adenosines than long RNAs, loops decrease the number of deaminations within an RNA by dividing a long RNA into shorter substrates. For a series of symmetric internal loops related in sequence, larger loops (greater than or equal to six nucleotides) acted as helix ends, whereas smaller loops (less than or equal to four nucleotides) did not. Our work provides the first information about how secondary structure within ADAR substrates dictates selectivity, and suggests a rational approach for delineating minimal substrates for RNAs deaminated by ADARs in vivo. (C) 1999 Academic Press.