Genome-wide analysis of mRNA targets for Caenorhabditis elegans FBF, a conserved stem cell regulator
Genome-wide analysis of mRNA targets for Caenorhabditis elegans FBF, a conserved stem cell regulator
复制标题
DOI：
10.1073/pnas.1000495107
复制
发表时间：
2010-02-23
影响因子：
11.1
通讯作者：
Kimble, Judith
中科院分区：
文献类型：
--
作者：
Kershner, Aaron M.;Kimble, Judith
在多细胞生物的发育过程中，干细胞对于组织的生成和成人的组织稳态是必不可少的。干细胞巨大的治疗前景使理解它们的调控成为高度优先事项。PUF RNA结合蛋白在促进生殖系干细胞自我更新方面具有保守的作用。在这里，我们使用全基因组的方法来识别秀丽线虫PUF蛋白(FBF)的假定目标mRNAs。我们发现，假定的FBF靶标代表了线虫所有蛋白质编码基因的7%，这意味着FBF是一个广谱的基因调节因子。这些假定的FBF靶标对于减数分裂进入的调节因子和减数分裂计划的其他组成部分以及关键发育途径的调节因子都是丰富的。我们认为，这些靶点可能对FBF在干细胞维持中的作用至关重要。将可能的FBF靶基因与果蝇和人类的PUF靶基因进行比较，发现了40个共同的靶基因，其中包括几个已建立的干细胞调节因子。我们推测，共享的PUF靶点代表了广泛使用的干细胞控制模块的一部分。
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 similar to 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.