The GLD-2 poly(A) polymerase activates gld-1 mRNA in the Caenorhabditis elegans germ line

Abstract

mRNA regulation is crucial for many aspects of metazoan development and physiology, including regulation of stem cells and synaptic plasticity. In the nematode germ line, RNA regulators control stem cell maintenance, the sperm͞oocyte decision, and progression through meiosis. Of particular importance to this work are three GLD (germ-line development) regulatory proteins, each of which promotes entry into the meiotic cell cycle: GLD-1 is a STAR͞Quaking translational repressor, GLD-2 is a cytoplasmic poly(A) polymerase, and GLD-3 is a homolog of Bicaudal-C. Here we report that the gld-1 mRNA is a direct target of the GLD-2 poly(A) polymerase: polyadenylation of gld-1 mRNA depends on GLD-2, the abundance of GLD-1 protein is dependent on GLD-2, and the gld-1 mRNA coimmunoprecipitates with both GLD-2 and GLD-3 proteins. We suggest that the GLD-2 poly(A) polymerase enhances entry into the meiotic cell cycle at least in part by activating GLD-1 expression. The importance of this conclusion is twofold. First, the activation of gld-1 mRNA by GLD-2 identifies a positive regulatory step that reinforces the decision to enter the meiotic cell cycle. Second, gld-1 mRNA is initially repressed by FBF (for fem-3 binding factor) to maintain stem cells but then becomes activated by the GLD-2 poly(A) polymerase once stem cells begin to make the transition into the meiotic cell cycle. Therefore, a molecular switch regulates gld-1 mRNA activity to accomplish the transition from mitosis to meiosis. cytoplasmic poly(A) polymerase ͉ RNA regulation ͉ mitosis͞meiosis decision

Negative Regulation of Meiotic Gene Expression by the Nuclear Poly(a)-binding Protein in Fission Yeast

“…A polyadenylationdependent mechanism has been previously established during the mitosis-meiosis decision in the Caenorhabditis elegans germ line. In this organism, a regulatory cytoplasmic polyadenylation complex stimulates the expression of meiotic genes (46,47). Whereas this cytoplasmic pathway represents a positive regulatory step that reinforces commitment to the meiotic cycle in C. elegans, the Pab2-dependent mechanism described in this study is nuclear and represents a negative regulatory step to prevent untimely expression of meiotic genes.…”

mir-35 is involved in intestine cell G1/S transition and germ cell proliferation in C. elegans

“…It is known that GLP-1/Notch signaling is both necessary and sufficient for germline proliferation at the expense of differentiation, while Gld-1 inhibits germline mitosis and negative feedback regulates GLP-1/Notch signaling [53][54][55]. In the mitotic region, GLP-1 proteins are present close to where DTC is [56,57], while GLD-1 is present close to the transition zone [24,26], making gld-1 a top candidate gene responsible for the loss of germ cells in gk262. Indeed, our experiments indicate that mir-35 directly targets gld-1 and a higher than normal level of GLD-1 inhibits germ cell mitosis (Figures 4 and 5).…”

“…In the gonad, GLP-1 (abnormal Germ Line Proliferation)/Notch signaling is essential to promote germ line divisions in distal mitotic region [19][20][21][22]. GLD (defective in Germ Line Development) family plays a key role in determining meiosis entry and indirectly regulates mitotic proliferation of the germline [23][24][25][26][27]. We found that mir-35 may down-regulate gld-1 to ensure a normal germline proliferation in distal the mir-35 mutant gk262, less intestinal nuclei were observed than the wide type, at 3-fold and L3/L4 stages, respectively (Table 1, P < 0.001, Student t-test).…”

A novel candidate cis-regulatory motif pair in the promoters of germline and oogenesis genes in C. elegans

“…Many of the germline-expressed genes were shown to function in meiotic processes, such as chromosome pairing, recombination, and segregation (e.g., zim-1, zim-2, zim-3, him-3, him-8). Additional known genes identified are gld-2, which encodes a translational activator (Suh et al 2006), and nos-3, which encodes a member of the Nanos family of RNA-binding proteins (Hansen et al 2004)-both are key regulators of entry into meiosis (Kimble and Crittenden 2007).…”