Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Development. 2012 Oct;139(20):3732-40. doi: 10.1242/dev.083980.
In the C. elegans germline, maintenance of undifferentiated stem cells depends on the PUF family RNA-binding proteins FBF-1 and FBF-2. FBF-1 and FBF-2 are 89% identical and are required redundantly to silence the expression of mRNAs that promote meiosis. Here we show that, despite their extensive sequence similarity, FBF-1 and FBF-2 have different effects on target mRNAs. FBF-1 promotes the degradation and/or transport of meiotic mRNAs out of the stem cell region, whereas FBF-2 prevents translation. FBF-2 activity depends on the P granule component PGL-1. PGL-1 is required to localize FBF-2 to perinuclear P granules and for efficient binding of FBF-2 to its mRNA targets. We conclude that multiple regulatory mechanisms converge on meiotic RNAs to ensure silencing in germline stem cells. Our findings also support the view that P granules facilitate mRNA silencing by providing an environment in which translational repressors can encounter their mRNA targets immediately upon exit from the nucleus.
在秀丽隐杆线虫的生殖系中，未分化干细胞的维持依赖于 PUF 家族 RNA 结合蛋白 FBF-1 和 FBF-2。FBF-1 和 FBF-2 有 89%的相同性，并且冗余地需要沉默促进减数分裂的 mRNA 的表达。在这里，我们表明，尽管它们具有广泛的序列相似性，但 FBF-1 和 FBF-2 对靶 mRNA 有不同的影响。FBF-1 促进减数分裂 mRNA 从干细胞区域降解和/或运输，而 FBF-2 则阻止翻译。FBF-2 的活性取决于 P 颗粒成分 PGL-1。PGL-1 需要将 FBF-2 定位到核周 P 颗粒，并使 FBF-2 与其 mRNA 靶标有效结合。我们得出结论，多种调节机制集中在减数分裂 RNA 上，以确保生殖干细胞中的沉默。我们的发现还支持 P 颗粒通过提供一种环境，使翻译抑制剂在从核中出来后立即遇到其 mRNA 靶标，从而促进 mRNA 沉默的观点。
