McJunkin Katherine, Ambros Victor
Program in Molecular Medicine, RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Genes Dev. 2017 Feb 15;31(4):422-437. doi: 10.1101/gad.290155.116. Epub 2017 Mar 9.
Gene expression in early animal embryogenesis is in large part controlled post-transcriptionally. Maternally contributed microRNAs may therefore play important roles in early development. We elucidated a major biological role of the nematode family of maternally contributed essential microRNAs. We show that this microRNA family regulates the sex determination pathway at multiple levels, acting both upstream of and downstream from to prevent aberrantly activated male developmental programs in hermaphrodite embryos. Both of the predicted target genes that act downstream from the family in this process, () and (NCL-1, HT2A, and LIN-41 repeat) domain-containing-2 (), encode RNA-binding proteins, thus delineating a previously unknown post-transcriptional regulatory subnetwork within the well-studied sex determination pathway of Repression of by the family is required for not only proper sex determination but also viability, showing that a single microRNA target site can be essential. Since sex determination in requires zygotic gene expression to read the sex chromosome karyotype, early embryos must remain gender-naïve; our findings show that the family microRNAs act in the early embryo to function as a developmental timer that preserves naïveté and prevents premature deleterious developmental decisions.
在动物胚胎发育早期，基因表达在很大程度上受到转录后调控。因此，母源提供的微小RNA可能在早期发育中发挥重要作用。我们阐明了线虫中母源提供的必需微小RNA家族的一个主要生物学功能。我们发现这个微小RNA家族在多个水平上调控性别决定途径，在tra-1的上游和下游发挥作用，以防止雌雄同体胚胎中异常激活的雄性发育程序。在此过程中，预测在该家族下游起作用的两个靶基因，sdc-2（含SET和环指结构域蛋白2）和ncl-1（NCL-1、HT2A和LIN-41重复序列）结构域含2（ncl-2），都编码RNA结合蛋白，从而在已被充分研究的秀丽隐杆线虫性别决定途径中描绘出一个以前未知的转录后调控子网。该家族对tra-1的抑制不仅是正确性别决定所必需的，也是生存能力所必需的，这表明单个微小RNA靶位点可能是至关重要的。由于秀丽隐杆线虫的性别决定需要合子基因表达来读取性染色体核型，早期胚胎必须保持性别未分化状态；我们的研究结果表明，该家族微小RNA在早期胚胎中起作用，作为一个发育定时器，维持未分化状态并防止过早做出有害的发育决定。
