RNA hairpins in noncoding regions of human brain and Caenorhabditis elegans mRNA are edited by adenosine deaminases that act on RNA
RNA hairpins in noncoding regions of human brain and Caenorhabditis elegans mRNA are edited by adenosine deaminases that act on RNA
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DOI：
10.1073/pnas.112704299
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发表时间：
2002-06-11
影响因子：
11.1
通讯作者：
Bass, BL
中科院分区：
文献类型：
--
作者：
Morse, DP;Aruscavage, PJ;Bass, BL
作用于RNA的腺苷脱氨酶（ADAR）构成RNA编辑酶家族，其在RNA的双链区域内将腺苷转化为肌苷。我们以前开发了一种方法来识别含肌苷的RNA，并使用它来识别五个阿达尔底物在Calciumhabditis elegans。在这里，我们使用相同的方法来确定五个额外的线虫底物，包括三个mRNA编码蛋白质已知影响神经元功能。所有10种线虫底物都在位于非编码区的长茎环结构中进行编辑，因此与先前鉴定的其他生物体的底物形成对比，其中ADAR靶向密码子。为了确定非编码区的编辑是否是一种保守的阿达尔功能，我们将我们的方法应用于人脑的poly（A）（+）RNA，并鉴定了19种以前未知的ADAIR底物。这些底物与在线虫中观察到的底物惊人地相似，因为编辑仅限于3'非翻译区、内含子和非编码RNA。同样与在秀丽隐杆线虫中发现的相似，19种底物中有15种在重复元件中进行了编辑。新发现的阿达尔底物的身份表明，RNA编辑可能会影响许多生物学上重要的过程，对于许多后生动物，编码区的A到I转换可能是例外，而不是规则。
Adenosine deaminases that act on RNA (ADARs) constitute a family of RNA-editing enzymes that convert adenosine to inosine within double-stranded regions of RNA. We previously developed a method to identify inosine-containing RNAs and used it to identify five ADAR substrates in Calenorhabditis elegans. Here we use the same method to identify five additional C elegans substrates, including three mRNAs that encode proteins known to affect neuronal functions. All 10 of the C elegans substrates are edited in long stem-loop structures located in noncoding regions, and thus contrast with previously identified substrates of other organisms, in which ADARs target codons. To determine whether editing in noncoding regions was a conserved ADAR function, we applied our method to poly(A)(+) RNA of human brain and identified 19 previously unknown ADAIR substrates. The substrates were strikingly similar to those observed in C elegans, since editing was confined to 3' untranslated regions, introns, and a noncoding RNA. Also similar to what was found in C elegans, 15 of the 19 substrates were edited in repetitive elements. The identities of the newly identified ADAR substrates suggest that RNA editing may influence many biologically important processes, and that for many metazoa, A-to-I conversion in coding regions may be the exception rather than the rule.