Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida 32610, USA.
UF Genetics Institute, University of Florida, Gainesville, Florida 32610, USA.
RNA. 2021 Jun;27(6):694-709. doi: 10.1261/rna.078694.121. Epub 2021 Apr 1.
MicroRNAs (miRNAs) are small noncoding RNAs that function as critical posttranscriptional regulators in various biological processes. While most miRNAs are generated from processing of long primary transcripts via sequential Drosha and Dicer cleavage, some miRNAs that bypass Drosha cleavage can be transcribed as part of another small noncoding RNA. Here, we develop the arget-riented RNA iscovery (TOMiD) bioinformatic analysis method to identify Drosha-independent miRNAs from ronaute rossinking nd equencing of ybrids (Ago-CLASH) data sets. Using this technique, we discovered a novel miRNA derived from a primate specific noncoding RNA, the small NF90 associated RNA A (snaR-A). The miRNA derived from snaR-A (miR-snaR) arises independently of Drosha processing but requires Exportin-5 and Dicer for biogenesis. We identify that miR-snaR is concurrently up-regulated with the full snaR-A transcript in cancer cells. Functionally, miR-snaR associates with Ago proteins and targets NME1, a key metastasis inhibitor, contributing to snaR-A's role in promoting cancer cell migration. Our findings suggest a functional link between a novel miRNA and its precursor noncoding RNA.
微小 RNA（miRNAs）是一类小的非编码 RNA，作为关键的转录后调控因子在各种生物学过程中发挥作用。虽然大多数 miRNAs 是通过 Drosha 和 Dicer 连续切割长的初级转录物而产生的，但一些绕过 Drosha 切割的 miRNAs 可以作为另一种小非编码 RNA 的一部分转录。在这里，我们开发了靶向 RNA 发现（TOMiD）生物信息学分析方法，用于从 Ronaute 交联和杂交（Ago-CLASH）数据集的 RNA 测序数据中识别 Drosha 非依赖性 miRNAs。使用这项技术，我们发现了一种源自灵长类动物特异性非编码 RNA 小 NF90 相关 RNA A（snaR-A）的新型 miRNA。源自 snaR-A 的 miRNA（miR-snaR）的产生不依赖于 Drosha 加工，但需要 Exportin-5 和 Dicer 进行生物发生。我们发现，miR-snaR 在癌细胞中与全长 snaR-A 转录物同时上调。在功能上，miR-snaR 与 Ago 蛋白结合，并靶向 NME1，一种关键的转移抑制剂，这有助于 snaR-A 在促进癌细胞迁移中的作用。我们的研究结果表明，一种新型 miRNA 与其前体非编码 RNA 之间存在功能联系。
