Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Department of Molecular and Computational Biology, Dornsife College of Letters, Arts, and Science, University of Southern California, Los Angeles, CA, USA.
Sci Rep. 2020 Nov 9;10(1):19367. doi: 10.1038/s41598-020-76423-5.
The negative regulator of RNA polymerase (pol) III mafr-1 has been shown to affect RNA pol III transcript abundance, lipid biosynthesis and storage, progeny output, and lifespan. We deleted mafr-1 from the Caenorhabditis elegans genome and found that animals lacking mafr-1 replicated many phenotypes from previous RNAi-based studies and discovered a new sperm-specific role. Utilizing a yeast two-hybrid assay, we discovered several novel interactors of MAFR-1 that are expressed in a sperm- and germline-enriched manner. In support of a role for MAFR-1 in the male germline, we found mafr-1 null males have smaller spermatids that are less capable in competition for fertilization; a phenotype that was dependent on RNA pol III activity. Restoration of MAFR-1 expression specifically in the germline rescued the spermatid-related phenotypes, suggesting a cell autonomous role for MAFR-1 in nematode male fertility. Based on the high degree of conservation of Maf1 activity across species, our study may inform similar roles for Maf1 and RNA pol III in mammalian male fertility.
RNA 聚合酶 III（pol）III 的负调控因子 mafr-1 已被证明会影响 RNA pol III 转录物丰度、脂质生物合成和储存、后代产量和寿命。我们从秀丽隐杆线虫的基因组中删除了 mafr-1，发现缺乏 mafr-1 的动物复制了之前基于 RNAi 的研究中的许多表型，并发现了一个新的精子特异性作用。利用酵母双杂交测定，我们发现了几种新型 MAFR-1 的相互作用因子，这些因子以精子和生殖系丰富的方式表达。支持 MAFR-1 在雄性生殖系中的作用，我们发现 mafr-1 缺失的雄性具有更小的精子，在受精竞争中能力较低；这一表型依赖于 RNA pol III 活性。特异性在生殖系中恢复 MAFR-1 的表达挽救了与精子相关的表型，表明 MAFR-1 在线虫雄性生育力中具有细胞自主作用。基于 Maf1 活性在物种间的高度保守性，我们的研究可能为 Maf1 和 RNA pol III 在哺乳动物雄性生育力中的类似作用提供信息。
