Institute of Molecular Medicine, College of Medicine, National Taiwan University, No. 7 Chung-Shan South Road, Taipei 10002, Taiwan.
Center of Precision Medicine, College of Medicine, National Taiwan University, No. 7 Chung-Shan South Road, Taipei 10002, Taiwan.
Sci Adv. 2022 Aug 12;8(32):eabm0699. doi: 10.1126/sciadv.abm0699. Epub 2022 Aug 10.
Small RNAs regulate spermatogenesis across species ranging from to humans. In , two Argonaute proteins, ALG-3 and ALG-4, and their associated 26G-small RNAs are essential for spermiogenesis at 25°C. The 26G-small RNAs are antisense to their target mRNAs and produced by the RNA-dependent RNA polymerase, RRF-3. However, it remains unclear how the RNA templates for RRF-3 are generated and which cellular processes are affected by 26G-small RNAs. Here, we demonstrate a previously unidentified zc3h12a-like ribonuclease protein, NYN-3, in 26G-small RNAs biogenesis. NYN-3 is not only required for proper abundance of 26G-small RNAs but also crosslinked to their targeted mRNAs before RRF-3 from ePAR-CLIP-seq. Bioinformatics analysis was then used to parse the 26G-small RNA-targeted genes into functional subclasses. Collectively, these findings implicate NYN-3 as an initiator of 26G-small RNA generation.
小 RNA 调节从 到人类等各种物种的精子发生。在 中,两种 Argonaute 蛋白(ALG-3 和 ALG-4)及其相关的 26G-小 RNA 对于 25°C 下的精子发生至关重要。26G-小 RNA 与它们的靶 mRNA 是反义的,由 RNA 依赖性 RNA 聚合酶 RRF-3 产生。然而,目前尚不清楚 RRF-3 的 RNA 模板是如何产生的,以及哪些细胞过程受到 26G-小 RNA 的影响。在这里,我们证明了在 26G-小 RNA 生物发生中存在一种先前未被识别的 zc3h12a 样核糖核酸酶蛋白 NYN-3。NYN-3 不仅是 26G-小 RNA 适当丰度所必需的,而且在 ePAR-CLIP-seq 中,NYN-3 还与它们的靶 mRNA 交联。然后,我们使用生物信息学分析将 26G-小 RNA 靶向基因解析为功能亚类。总的来说,这些发现表明 NYN-3 是 26G-小 RNA 产生的启动子。