AUTHOR=Park Youngyong , O’Rourke Samuel , Taki Faten A. , Alfhili Mohammad A. , Lee Myon Hee 

TITLE=Dose-Dependent Effects of GLD-2 and GLD-1 on Germline Differentiation and Dedifferentiation in the Absence of PUF-8

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00005

DOI=10.3389/fcell.2020.00005

ISSN=2296-634X

ABSTRACT=<p>PUMILIO/FBF (PUF) proteins have a conserved function in stem cell regulation. <italic>Caenorhabditis elegans</italic> PUF-8 protein inhibits the translation of target mRNAs by interacting with PUF binding element (PBE) in the 3′ untranslated region (3′ UTR). In this work, an <italic>in silico</italic> analysis has identified <italic>gld-2</italic> [a poly(A) polymerase] as a putative PUF-8 target. Biochemical and reporter analyses showed that PUF-8 specifically binds to a PBE in <italic>gld-2</italic> 3′ UTR and represses a GFP reporter gene carrying <italic>gld-2</italic> 3′ UTR in the <italic>C. elegans</italic> mitotic germ cells. GLD-2 enhances meiotic entry at least in part by activating GLD-1 (a KH motif-containing RNA-binding protein). Our genetic analyses also demonstrated that heterozygous <italic>gld-2(+/−) gld-1(+/−)</italic> genes in the absence of PUF-8 are competent for meiotic entry (early differentiation), but haplo-insufficient for the meiotic division (terminal differentiation) of spermatocytes. Indeed, the arrested spermatocytes return to mitotic cells via dedifferentiation, which results in germline tumors. Since these regulators are broadly conserved, we thus suggest that similar molecular mechanisms may control differentiation, dedifferentiation, and tumorigenesis in other organisms, including humans.</p>