RT Journal Article SR Electronic T1 LST-1 acts in trans with a conserved RNA-binding protein to maintain stem cells JF bioRxiv FD Cold Spring Harbor Laboratory SP 657312 DO 10.1101/657312 A1 Kimberly A. Haupt A1 Amy L. Enright A1 Ahlan S. Ferdous A1 Aaron M. Kershner A1 Heaji Shin A1 Marvin Wickens A1 Judith Kimble YR 2019 UL http://biorxiv.org/content/early/2019/06/03/657312.abstract AB Stem cell self-renewal is essential to development and tissue repair. The C. elegans LST-1 protein is a pivotal regulator of self-renewal and oncogenic when misexpessed. Here we define regions within the LST-1 protein that provide molecular insights into both its function and regulation. LST-1 self-renewal activity resides within a predicted disordered region that harbors two KXXL motifs. These KXXL motifs mediate LST-1 binding to FBF, a broadly conserved Pumilio/PUF RNA-binding protein that represses differentiation. Point mutations of the KXXL motifs abrogate LST-1 self-renewal activity. Therefore, FBF binding is essential to LST-1 function. A second distinct region regulates LST-1 spatial expression and primarily affects LST-1 protein turnover. Upon loss of this regulatory region, LST-1 protein distribution expands and drives formation of a larger than normal GSC pool. Thus, LST-1 promotes self-renewal as a key FBF partner, and its spatial regulation helps determine size of the GSC pool.IMPACT STATEMENT A key stem cell regulator partners with a broadly conserved PUF RNA-binding protein to drive self-renewal and maintain a stem cell pool.