Widespread cytoplasmic polyadenylation programs asymmetry in the germline and early embryo

Abstract

BACKGROUND:The program of embryonic development is launched by selective activation of a silent maternal transcriptome. In Caenorhabditis elegans, nuclei of the adult germline are responsible for the synthesis of at least two distinct mRNA populations; those required for housekeeping functions, and those that program the oocyte-to-embryo transition. We mapped this separation by changes to the length-distribution of poly(A)-tails that depend on GLD-2 mediated cytoplasmic polyadenylation and its regulators genome-wide. RESULTS:More than 1000 targets of cytoplasmic polyadenylation were identified by differential polyadenylation. Amongst mRNA with the greatest dependence on GLD-2 were those encoding RNA binding proteins with known roles in spatiotemporal patterning such as mex-5 and pos-1. In General, the 3' UTR of GLD-2 targets were longer, contained cytosine-patches, and were enriched for non-standard polyadenylation-motifs. To identify the deadenylase that initiated transcript silencing, we depleted the known deadenylases in the gld-2(0) mutant background. Only the loss of CCF-1 suppressed the short-tailed phenotype of GLD-2 targets suggesting that in addition to its general role in RNA turnover, this is the major deadenylase for regulatory silencing of maternal mRNA. Analysis of poly(A)-tail length-change in the embryo lacking specific RNA-binding proteins revealed new candidates for asymmetric expression in the first embryonic divisions. CONCLUSION:The concerted action of RNA binding proteins exquisitely regulates GLD-2 activity in space and time. We present our data as interactive web resources for a model where GLD-2 mediated cytoplasmic polyadenylation regulates target mRNA at each stage of worm germline and early embryonic development.

TENT-5 regulates the expression of male-specific genes inCaenorhabditis elegans

“…In C. elegans , GLD-2 is a crucial regulator of the germline mitosis-to-meiosis transition and subsequent gametogenesis (20). Consequently, GLD-2 depletion in nematodes results in defective oocytes and sperm production, leading to infertility in both hermaphrodites and males (22). Similarly, two homologs of GLD-2 in D. melanogaster , Gld2 and Wispy, are essential for proper gamete production in a sex-dependent manner (23, 24).…”

“…Moreover, poly(A) tail dynamics is affected by additional layers of regulatory control, including poly(A)-modifying enzymes that influence numerous physiological processes. For example, cytoplasmic polyadenylation by GLD2 (Germ Line Development 2)/TENT2 is indispensable for proper germline development and fertility in nematodes (20–22) and flies (23, 24). In mammals, a similar role is observed for the recently discovered TENT5 ncPAPs (15).…”