Okamura Katsutomo, Hagen Joshua W, Duan Hong, Tyler David M, Lai Eric C
Memorial Sloan-Kettering Cancer Center, Department of Developmental Biology, 1275 York Ave, Box 252, New York, NY 10021, USA.
Cell. 2007 Jul 13;130(1):89-100. doi: 10.1016/j.cell.2007.06.028. Epub 2007 Jun 28.
The canonical microRNA (miRNA) pathway converts primary hairpin precursor transcripts into approximately 22 nucleotide regulatory RNAs via consecutive cleavages by two RNase III enzymes, Drosha and Dicer. In this study, we characterize Drosophila small RNAs that derive from short intronic hairpins termed "mirtrons." Their nuclear biogenesis appears to bypass Drosha cleavage, which is essential for miRNA biogenesis. Instead, mirtron hairpins are defined by the action of the splicing machinery and lariat-debranching enzyme, which yield pre-miRNA-like hairpins. The mirtron pathway merges with the canonical miRNA pathway during hairpin export by Exportin-5, and both types of hairpins are subsequently processed by Dicer-1/loqs. This generates small RNAs that can repress perfectly matched and seed-matched targets, and we provide evidence that they function, at least in part, via the RNA-induced silencing complex effector Ago1. These findings reveal that mirtrons are an alternate source of miRNA-type regulatory RNAs.
经典的微小RNA（miRNA）途径通过两种核糖核酸酶III（RNase III）酶Drosha和Dicer的连续切割，将初级发夹前体转录本转化为约22个核苷酸的调控RNA。在本研究中，我们鉴定了源自称为“mirtrons”的短内含子发夹的果蝇小RNA。它们的核生物合成似乎绕过了对miRNA生物合成至关重要的Drosha切割。相反，mirtron发夹由剪接机制和套索脱支酶的作用定义，这些酶产生类似前体miRNA的发夹。在Exportin-5介导的发夹输出过程中，mirtron途径与经典miRNA途径合并，随后两种类型的发夹都由Dicer-1/loqs进行加工。这产生了可以抑制完全匹配和种子匹配靶标的小RNA，并且我们提供的证据表明它们至少部分地通过RNA诱导沉默复合体效应因子Ago1发挥作用。这些发现揭示了mirtrons是miRNA型调控RNA的另一种来源。
