A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans
A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans
复制标题
DOI：
10.1038/nature754
复制
发表时间：
2002-06-06
期刊：
影响因子：
64.8
通讯作者：
Kimble, J
中科院分区：
文献类型：
--
作者：
Crittenden, SL;Bernstein, DS;Kimble, J
生殖系干细胞的定义是它们独特的能力，产生更多的自己以及分化的配子（1）。控制自我更新和分化之间的决定的分子机制是发育生物学中未解决的问题，具有潜在的广泛的医学意义。在秀丽隐杆线虫中，生殖系干细胞由体细胞远端细胞控制（2，3）。FBF-1和FBF-2是两种几乎相同的蛋白质，它们一起被称为FBF（“fem-3 mRNA结合因子”），最初被发现是生殖系性别决定的调节因子（4）。在这里，我们报告说，FBF也控制生殖干细胞：在一个fbf-1 fbf-2双突变体，生殖细胞增殖最初是正常的，但干细胞不维持。我们认为FBF至少部分通过抑制gld-1来控制生殖系干细胞，而gld-1本身促进减数分裂细胞周期的定型（5，6）。FBF属于RNA结合蛋白的PUF家族（“Pumilio和FBF”）（7）。Pumilio控制果蝇雌性中的生殖系干细胞（8，9），并且在低等真核生物中，PUF蛋白促进持续的有丝分裂（10，11）。我们认为PUF蛋白的调控可能是一种古老而广泛的干细胞调控机制。
Germline stem cells are defined by their unique ability to generate more of themselves as well as differentiated gametes(1). The molecular mechanisms controlling the decision between self-renewal and differentiation are central unsolved problems in developmental biology with potentially broad medical implications. In Caenorhabditis elegans, germline stem cells are controlled by the somatic distal tip cell(2,3). FBF-1 and FBF-2, two nearly identical proteins, which together are called FBF ('fem-3 mRNA binding factor'), were originally discovered as regulators of germline sex determination(4). Here we report that FBF also controls germline stem cells: in an fbf-1 fbf-2 double mutant, germline proliferation is initially normal, but stem cells are not maintained. We suggest that FBF controls germline stem cells, at least in part, by repressing gld-1, which itself promotes commitment to the meiotic cell cycle(5,6). FBF belongs to the PUF family ('Pumilio and FBF') of RNA-binding proteins(7). Pumilio controls germline stem cells in Drosophila females(8,9),and, in lower eukaryotes, PUF proteins promote continued mitoses(10,11). We suggest that regulation by PUF proteins may be an ancient and widespread mechanism for control of stem cells.