Department of Biochemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Genome Res. 2012 Aug;22(8):1488-98. doi: 10.1101/gr.134841.111. Epub 2012 Jun 6.
Adenosine deaminases that act on RNA (ADARs) are RNA editing enzymes that convert adenosine to inosine in double-stranded RNA (dsRNA). To evaluate effects of ADARs on small RNAs that derive from dsRNA precursors, we performed deep-sequencing, comparing small RNAs from wild-type and ADAR mutant Caenorhabditis elegans. While editing in small RNAs was rare, at least 40% of microRNAs had altered levels in at least one ADAR mutant strain, and miRNAs with significantly altered levels had mRNA targets with correspondingly affected levels. About 40% of siRNAs derived from endogenous genes (endo-siRNAs) also had altered levels in at least one mutant strain, including 63% of Dicer-dependent endo-siRNAs. The 26G class of endo-siRNAs was significantly affected by ADARs, and many altered 26G loci had intronic reads and histone modifications associated with transcriptional silencing. Our data indicate that ADARs, through both direct and indirect mechanisms, are important for maintaining wild-type levels of many small RNAs in C. elegans.
作用于 RNA 的腺苷脱氨酶(ADARs)是 RNA 编辑酶,可将双链 RNA(dsRNA)中的腺苷转化为肌苷。为了评估 ADAR 对源自 dsRNA 前体的小 RNA 的影响,我们进行了深度测序,比较了来自野生型和 ADAR 突变型秀丽隐杆线虫的小 RNA。虽然小 RNA 中的编辑很少,但至少有 40%的 microRNA 在至少一种 ADAR 突变株中水平发生改变,并且水平显著改变的 miRNA 具有相应水平改变的 mRNA 靶标。至少有一种突变株中,约 40%源自内源性基因(endo-siRNAs)的 siRNA 水平也发生了改变,包括 63%依赖于 Dicer 的 endo-siRNAs。26G 类 endo-siRNA 受到 ADARs 的显著影响,许多改变的 26G 位置具有与转录沉默相关的内含子读取和组蛋白修饰。我们的数据表明,ADARs 通过直接和间接机制,对于维持秀丽隐杆线虫中许多小 RNA 的野生型水平非常重要。