Qiu Chen, Crittenden Sarah L, Carrick Brian H, Dillard Lucas B, Costa Dos Santos Stephany J, Dandey Venkata P, Dutcher Robert C, Viverette Elizabeth G, Wine Robert N, Woodworth Jennifer, Campbell Zachary T, Wickens Marvin, Borgnia Mario J, Kimble Judith, Tanaka Hall Traci M
Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
bioRxiv. 2024 Jun 14:2024.06.14.599074. doi: 10.1101/2024.06.14.599074.
PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including . Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses via a pair of adjacent FBF-2 binding elements (FBEs) in its 3ÚTR. One LST-1 molecule links two FBF-2 molecules via motifs in the LST-1 intrinsically-disordered region; the FBE pair includes a well-established 'canonical' FBE and a newly-identified noncanonical FBE. Remarkably, this FBE pair drives both full RNA repression in GSCs and full RNA activation upon differentiation. Discovery of the LST-1-FBF-2 ternary complex, the adjacent FBEs, and their significance predicts an expanded regulatory repertoire of different assemblies of PUF-partner complexes in nematode germline stem cells. It also suggests analogous PUF controls may await discovery in other biological contexts and organisms.
PUF RNA结合蛋白是广泛保守的干细胞调节因子。线虫PUF蛋白维持生殖系干细胞（GSCs），并与关键伴侣蛋白一起抑制分化mRNA，包括……。在这里，我们报告PUF蛋白FBF-2及其伴侣LST-1形成三元复合物，该复合物通过其3′UTR中的一对相邻FBF-2结合元件（FBEs）抑制……。一个LST-1分子通过LST-1内在无序区域中的基序连接两个FBF-2分子；FBE对包括一个公认的“经典”FBE和一个新鉴定的非经典FBE。值得注意的是，这对FBE在GSCs中驱动完全的RNA抑制，在分化时驱动完全的RNA激活。LST-1-FBF-2三元复合物、相邻FBEs及其意义的发现预示着线虫生殖系干细胞中PUF-伴侣复合物不同组装的调节功能会有所扩展。这也表明在其他生物学背景和生物体中可能有待发现类似的PUF调控机制。
