Fischer Sylvia E J, Butler Maurice D, Pan Qi, Ruvkun Gary
Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Nature. 2008 Sep 25;455(7212):491-6. doi: 10.1038/nature07274. Epub 2008 Sep 10.
Mutations that enhance the response to double-stranded RNA (dsRNA) have revealed components of the RNA interference (RNAi) pathway or related small RNA pathways. To explore these small RNA pathways, we screened for Caenorhabditis elegans mutants displaying an enhanced response to exogenous dsRNAs. Here we describe the isolation of mutations in two adjacent, divergently transcribed open reading frames (eri-6 and eri-7) that fail to complement. eri-6 and eri-7 produce separate pre-messenger RNAs (pre-mRNAs) that are trans-spliced to form a functional mRNA, eri-6/7. Trans-splicing of eri-6/7 is mediated by a direct repeat that flanks the eri-6 gene. Adenosine to inosine editing within untranslated regions of eri-6 and eri-7 pre-mRNAs reveals a double-stranded pre-mRNA intermediate, forming in the nucleus before splicing occurs. The ERI-6/7 protein is a superfamily I helicase that both negatively regulates the exogenous RNAi pathway and functions in an endogenous RNAi pathway.
增强对双链RNA（dsRNA）反应的突变揭示了RNA干扰（RNAi）途径或相关小RNA途径的组成部分。为了探索这些小RNA途径，我们筛选了对外源dsRNA表现出增强反应的秀丽隐杆线虫突变体。在此，我们描述了两个相邻的、转录方向相反的开放阅读框（eri-6和eri-7）中不能互补的突变的分离。eri-6和eri-7产生单独的前体信使RNA（pre-mRNA），它们经反式剪接形成功能性mRNA，即eri-6/7。eri-6/7的反式剪接由eri-6基因两侧的一个直接重复序列介导。eri-6和eri-7前体mRNA非翻译区内的腺苷到肌苷编辑揭示了一种双链前体mRNA中间体，它在剪接发生之前在细胞核中形成。ERI-6/7蛋白是一个I类解旋酶超家族成员，它既对外源RNAi途径起负调控作用，又在内源RNAi途径中发挥作用。
