Novel Function of PUF Proteins and Their Partners in Spermatogenesis and Spermatocyte-Derived Germline Tumors in Caenorhabditis elegans

Abstract

Conserved PUF (Pumilio and FBF) proteins repress the translation by binding to its target mRNA 3' untranslated region (3'UTR). C. elegans has 11 PUF proteins. Among them, we focused on two FBFs (FBF-1 and FBF-2) and PUF-8. The object of this study is to identify a regulatory network including FBFs and PUF-8 in spermatogenesis and spermatocyte-derived germline tumors in vivo. Specifically, our significant findings are three-fold:1. FBFs and their repression target CYB-1 (B-type Cyclin) promote sperm viability by inhibiting CED-4 (an Apaf1 homolog)-mediated apoptosis (see Chapter 2)2. PUF-8 and its repression target, GLD-2 (a Cytoplasmic poly(A) polymerase) inhibit spermatocyte-derived tumorigenesis by activating GLD-1 (a KH motif-containing RNA-binding protein) and inhibiting MPK-1 (an ERK homolog) (see Chapter 3) 3. CYB-1 loss or X-ray irradiation could induce spermatocyte-derived germline tumors in the absence of PUF-8 and activation of MPK-1 (see Chapter 4). Since the regulators that we propose to study are broadly conserved, we therefore suggest that similar molecular mechanisms may control spermatogenesis and tumorigenesis in other organisms, including humans.