Gaylord Olivia J, Brown Jordan S, Wu Wei-Sheng, Lee Heng-Chi
Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL, 60637, USA.
Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, IL, 60637, USA.
bioRxiv. 2025 May 11:2025.05.11.653140. doi: 10.1101/2025.05.11.653140.
In germ cells, small RNAs function as a defense system to silence invading RNAs like viruses and transposons to protect genome integrity. The ability of small RNAs to robustly silence diverse RNA sequences prompts the question of how endogenous mRNAs avoid this silencing. In , small RNAs bound by the Argonaute CSR-1 protect endogenous mRNAs from silencing, while also fine-tuning a subset of these mRNAs. Here, we identify RNA Helicase A (RHA-1) as a key regulator of CSR-1 small RNA biogenesis and function in mRNA fine-tuning. RHA-1 localizes to germ granules dependent on EGO-1, which synthesizes CSR-1 small RNAs. We find RHA-1 promotes small RNA production from the 5' regions of mRNAs and small RNA sorting to CSR-1. Loss of RHA-1 leads to elevated CSR-1 target mRNA levels and compromised fertility. Our study highlights the importance of small RNA regulation, mediated by RHA-1, to protect endogenous gene expression programs and germ cell function.
在生殖细胞中，小RNA作为一种防御系统，使病毒和转座子等入侵RNA沉默，以保护基因组完整性。小RNA强大的使多种RNA序列沉默的能力引发了一个问题，即内源性mRNA如何避免这种沉默。在秀丽隐杆线虫中，与AGO蛋白CSR-1结合的小RNA保护内源性mRNA不被沉默，同时也对这些mRNA的一个子集进行微调。在这里，我们确定RNA解旋酶A（RHA-1）是CSR-1小RNA生物发生以及mRNA微调功能的关键调节因子。RHA-1依赖于合成CSR-1小RNA的EGO-1定位于生殖颗粒。我们发现RHA-1促进mRNA 5'区域的小RNA产生以及小RNA分选到CSR-1。RHA-1的缺失导致CSR-1靶标mRNA水平升高和生育能力受损。我们的研究强调了由RHA-1介导的小RNA调控对保护内源性基因表达程序和生殖细胞功能的重要性。
