Department of Biological Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, 521 A Physiology Building, Baltimore, MD, 21205, USA.
Nat Commun. 2018 Oct 2;9(1):4031. doi: 10.1038/s41467-018-06404-w.
Post-transcriptional regulation of gene expression plays an essential role during oocyte maturation. Here we report that Drosophila MARF1 (Meiosis Regulator And mRNA Stability Factor 1), which consists of one RNA-recognition motif and six tandem LOTUS domains with unknown molecular function, is essential for oocyte maturation. When tethered to a reporter mRNA, MARF1 post-transcriptionally silences reporter expression by shortening reporter mRNA poly-A tail length and thereby reducing reporter protein level. This activity is mediated by the MARF1 LOTUS domain, which binds the CCR4-NOT deadenylase complex. MARF1 binds cyclin A mRNA and shortens its poly-A tail to reduce Cyclin A protein level during oocyte maturation. This study identifies MARF1 as a regulator in oocyte maturation and defines the conserved LOTUS domain as a post-transcriptional effector domain that recruits CCR4-NOT deadenylase complex to shorten target mRNA poly-A tails and suppress their translation.
转录后基因表达调控在卵母细胞成熟过程中起着至关重要的作用。在这里,我们报告果蝇 MARF1(减数分裂调节因子和 mRNA 稳定性因子 1),它由一个 RNA 识别基序和六个串联 LOTUS 结构域组成,其分子功能尚不清楚,对卵母细胞成熟是必需的。当 MARF1 与报告 mRNA 结合时,通过缩短报告 mRNA 的 poly-A 尾长,从而降低报告蛋白水平,从而在后转录水平沉默报告基因的表达。这种活性是由 MARF1 的 LOTUS 结构域介导的,该结构域结合 CCR4-NOT 脱腺苷酸酶复合物。MARF1 结合细胞周期蛋白 A mRNA 并缩短其 poly-A 尾,以降低卵母细胞成熟过程中的 Cyclin A 蛋白水平。本研究鉴定 MARF1 为卵母细胞成熟的调节剂,并将保守的 LOTUS 结构域定义为一种在后转录水平起作用的效应结构域,它募集 CCR4-NOT 脱腺苷酸酶复合物来缩短靶 mRNA 的 poly-A 尾并抑制其翻译。