Department of Biological Sciences, Marquette University, 1428 W. Clybourn Ave, PO Box 1881, Milwaukee, WI 53233, USA.
Genetics. 2021 Mar 3;217(1):1-14. doi: 10.1093/genetics/iyaa006.
Posttranscriptional regulation of gene expression, typically effected by RNA-binding proteins, microRNAs (miRNAs), and translation initiation factors, is essential for normal germ cell function. Numerous miRNAs have been detected in the germline; however, the functions of specific miRNAs remain largely unknown. Functions of miRNAs have been difficult to determine as miRNAs often modestly repress target mRNAs and are suggested to sculpt or fine tune gene expression to allow for the robust expression of cell fates. In Caenorhabditis elegans hermaphrodites, cell fate decisions are made for germline sex determination during larval development when sperm are generated in a short window before the switch to oocyte production. Here, analysis of newly generated mir-44 family mutants has identified a family of miRNAs that modulate the germline sex determination pathway in C. elegans. Mutants with the loss of mir-44 and mir-45 produce fewer sperm, showing both a delay in the specification and formation of sperm as well as an early termination of sperm specification accompanied by a premature switch to oocyte production. mir-44 and mir-45 are necessary for the normal period of fog-1 expression in larval development. Through genetic analysis, we find that mir-44 and mir-45 may act upstream of fbf-1 and fem-3 to promote sperm specification. Our research indicates that the mir-44 family promotes sperm cell fate specification during larval development and identifies an additional posttranscriptional regulator of the germline sex determination pathway.
基因表达的转录后调控,通常由 RNA 结合蛋白、microRNAs(miRNAs)和翻译起始因子来完成,对于正常的生殖细胞功能至关重要。在线虫的生殖系中已经检测到许多 miRNAs,但特定 miRNAs 的功能仍然知之甚少。由于 miRNAs 通常会适度抑制靶 mRNA 的表达,并且被认为可以塑造或微调基因表达,以允许细胞命运的稳健表达,因此 miRNAs 的功能很难确定。在线虫的雌雄同体中,生殖细胞的命运决定是在幼虫发育过程中进行的,此时在向卵母细胞生成转变之前的一个短暂窗口中产生精子。在这里,对新生成的 mir-44 家族突变体的分析确定了一组 miRNA,它们在 C. elegans 中调节生殖细胞性别决定途径。mir-44 和 mir-45 缺失的突变体产生的精子较少,显示出精子的特化和形成延迟,以及精子特化的早期终止,伴随着卵母细胞生成的过早转变。mir-44 和 mir-45 对于幼虫发育过程中 fog-1 表达的正常时期是必要的。通过遗传分析,我们发现 mir-44 和 mir-45 可能在上游作用于 fbf-1 和 fem-3 以促进精子特化。我们的研究表明,mir-44 家族在幼虫发育过程中促进精子细胞命运特化,并确定了生殖细胞性别决定途径的另一个转录后调节剂。