Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003-Barcelona, Spain.
Universitat Pompeu Fabra (UPF), 08003-Barcelona, Spain.
RNA. 2018 Apr;24(4):529-539. doi: 10.1261/rna.065417.117. Epub 2018 Jan 9.
Cytoplasmic polyadenylation is a widespread mechanism to regulate mRNA translation. In vertebrates, this process requires two sequence elements in target 3' UTRs: the U-rich cytoplasmic polyadenylation element and the AAUAAA hexanucleotide. In , cytoplasmic polyadenylation of mRNA occurs independently of these canonical elements and requires a machinery that remains to be characterized. Here we identify Dicer-2 as a component of this machinery. Dicer-2, a factor previously involved in RNA interference (RNAi), interacts with the cytoplasmic poly(A) polymerase Wispy. Depletion of Dicer-2 from polyadenylation-competent embryo extracts and analysis of mutants indicate that both factors are necessary for polyadenylation and translation of mRNA. We further identify mRNA, encoding a Dicer-2 partner in RNAi, as a Dicer-2 polyadenylation target. Our results uncover a novel function of Dicer-2 in activation of mRNA translation through cytoplasmic polyadenylation.
细胞质多聚腺苷酸化是一种广泛存在的调节 mRNA 翻译的机制。在脊椎动物中，这个过程需要靶标 3'UTR 中的两个序列元件：富含 U 的细胞质多聚腺苷酸化元件和 AAUAAA 六核苷酸。在 中，mRNA 的细胞质多聚腺苷酸化独立于这些典型元件发生，并且需要一个尚未被鉴定的机制。在这里，我们鉴定 Dicer-2 为该机制的一个组成部分。Dicer-2 是一个先前参与 RNA 干扰 (RNAi) 的因子，与细胞质多聚(A)聚合酶 Wispy 相互作用。从多聚腺苷酸化能力的胚胎提取物中耗尽 Dicer-2 并分析 突变体表明，这两个因子对于 mRNA 的多聚腺苷酸化和翻译都是必需的。我们进一步鉴定出编码 RNAi 中 Dicer-2 伙伴的 mRNA 作为 Dicer-2 多聚腺苷酸化的靶标。我们的结果揭示了 Dicer-2 通过细胞质多聚腺苷酸化激活 mRNA 翻译的新功能。
