genome-wide analysis of gld-1–mediated mrna regulation suggests a role in mrna storage全基因组分析gld-1-mediated mrna在mrna存储监管建议的作用.pdfVIP

Genome-Wide Analysis of GLD-1–Mediated mRNA Regulation Suggests a Role in mRNA Storage ¤ Claudia Scheckel , Dimos Gaidatzis, Jane E. Wright, Rafal Ciosk* Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland Abstract Translational repression is often accompanied by mRNA degradation. In contrast, many mRNAs in germ cells and neurons are ‘‘stored’’ in the cytoplasm in a repressed but stable form. Unlike repression, the stabilization of these mRNAs is surprisingly little understood. A key player in Caenorhabditis elegans germ cell development is the STAR domain protein GLD-1. By genome- wide analysis of mRNA regulation in the germ line, we observed that GLD-1 has a widespread role in repressing translation but, importantly, also in stabilizing a sub-population of its mRNA targets. Additionally, these mRNAs appear to be stabilized by the DDX6-like RNA helicase CGH-1, which is a conserved component of germ granules and processing bodies. Because many GLD- 1 and CGH-1 stabilized mRNAs encode factors important for the oocyte-to-embryo transition (OET), our findings suggest that the regulation by GLD-1 and CGH-1 serves two purposes. Firstly, GLD-1–dependent repression prevents precocious translation of OET–promoting mRNAs. Secondly, GLD-1– and CGH-1–dependent stabilization ensures that these mRNAs are sufficiently abundant for robust translation when activated during OET. In the absence of this protective mechanism, the accumulation of OET–promoting mRNAs, and consequently the oocyte-to-embryo transition, might be compromised. Citation: Scheckel C, Gaidatzis D, Wright JE, Ciosk R (2012) Genome-Wide Analysis of GLD-1–Mediated mRNA Regulation Suggests a Role in mRNA Storage. PLoS Genet 8(5): e1002742. doi:10.1371/journal.pgen.1002742 Editor: Susan E. Mango, Harvard University, United States of America Received December 16, 2011; Accepted