Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3936-41. doi: 10.1073/pnas.1000495107. Epub 2010 Feb 8.
Stem cells are essential for tissue generation during the development of multicellular creatures, and for tissue homeostasis in adults. The great therapeutic promise of stem cells makes understanding their regulation a high priority. PUF RNA-binding proteins have a conserved role in promoting self-renewal of germline stem cells. Here we use a genome-wide approach to identify putative target mRNAs for the Caenorhabditis elegans PUF protein known as FBF. We find that putative FBF targets represent approximately 7% of all protein-coding genes in C. elegans, implicating FBF as a broad-spectrum gene regulator. These putative FBF targets are enriched for regulators of meiotic entry and other components of the meiotic program as well as regulators of key developmental pathways. We suggest that these targets may be critical for FBF's role in stem cell maintenance. Comparison of likely FBF target mRNAs with putative PUF target mRNAs from Drosophila and humans reveals 40 shared targets, including several established stem cell regulators. We speculate that shared PUF targets represent part of a broadly used module of stem cell control.
干细胞对于多细胞生物的组织生成以及成体组织的稳态至关重要。干细胞具有巨大的治疗潜力,这使得理解其调控机制成为当务之急。 PUF RNA 结合蛋白在促进生殖干细胞自我更新方面具有保守作用。在这里,我们使用全基因组方法来鉴定已知为 FBF 的秀丽隐杆线虫 PUF 蛋白的潜在靶 mRNA。我们发现,潜在的 FBF 靶标约占秀丽隐杆线虫所有编码蛋白基因的 7%,这表明 FBF 是一种广谱的基因调节剂。这些潜在的 FBF 靶标富含减数分裂起始的调节剂和减数分裂程序的其他成分以及关键发育途径的调节剂。我们认为这些靶标可能对 FBF 在干细胞维持中的作用至关重要。与果蝇和人类的潜在 PUF 靶标 mRNA 进行比较,发现了 40 个共享靶标,包括几个已确立的干细胞调节剂。我们推测共享的 PUF 靶标代表了干细胞控制的广泛使用模块的一部分。