Wang Liaoteng, Eckmann Christian R, Kadyk Lisa C, Wickens Marvin, Kimble Judith
Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Nature. 2002 Sep 19;419(6904):312-6. doi: 10.1038/nature01039.
Messenger RNA regulation is a critical mode of controlling gene expression. Regulation of mRNA stability and translation is linked to controls of poly(A) tail length. Poly(A) lengthening can stabilize and translationally activate mRNAs, whereas poly(A) removal can trigger degradation and translational repression. Germline granules (for example, polar granules in flies, P granules in worms) are ribonucleoprotein particles implicated in translational control. Here we report that the Caenorhabditis elegans gene gld-2, a regulator of mitosis/meiosis decision and other germline events, encodes the catalytic moiety of a cytoplasmic poly(A) polymerase (PAP) that is associated with P granules in early embryos. Importantly, the GLD-2 protein sequence has diverged substantially from that of conventional eukaryotic PAPs, and lacks a recognizable RRM (RNA recognition motif)-like domain. GLD-2 has little PAP activity on its own, but is stimulated in vitro by GLD-3. GLD-3 is also a developmental regulator, and belongs to the Bicaudal-C family of RNA binding proteins. We suggest that GLD-2 is the prototype for a class of regulatory cytoplasmic PAPs that are recruited to specific mRNAs by a binding partner, thereby targeting those mRNAs for polyadenylation and increased expression.
信使核糖核酸(mRNA)调控是控制基因表达的关键模式。mRNA稳定性和翻译的调控与多聚腺苷酸(poly(A))尾巴长度的控制相关。poly(A)延长可使mRNA稳定并激活其翻译,而poly(A)去除则可引发降解和翻译抑制。生殖系颗粒(例如,果蝇中的极性颗粒、线虫中的P颗粒)是参与翻译控制的核糖核蛋白颗粒。在此,我们报道秀丽隐杆线虫基因gld-2,它是有丝分裂/减数分裂决定及其他生殖系事件的调节因子,编码一种细胞质多聚(A)聚合酶(PAP)的催化部分,该酶在早期胚胎中与P颗粒相关联。重要的是,GLD-2蛋白序列与传统真核生物PAPs的序列有很大差异,并且缺乏可识别的类RNA识别基序(RRM)结构域。GLD-2自身的PAP活性很低,但在体外受到GLD-3的刺激。GLD-3也是一种发育调节因子,属于RNA结合蛋白的双尾-C家族。我们认为GLD-2是一类调节性细胞质PAPs的原型,它们通过结合伴侣被招募到特定的mRNA上,从而使这些mRNA进行多聚腺苷酸化并增加表达。