ADR-2 regulates fertility and oocyte fate in Caenorhabditis elegans

Author:

Erdmann Emily A1ORCID,Forbes Melanie2,Becker Margaret3,Perez Sarina2,Hundley Heather A2ORCID

Affiliation:

1. Genome, Cell and Developmental Biology Graduate Program, Indiana University , Bloomington, IN 47405 , USA

2. Department of Biology, Indiana University , Bloomington, IN 47405 , USA

3. Medical Sciences Program, Indiana University School of Medicine-Bloomington , Bloomington IN 47405 , USA

Abstract

Abstract RNA-binding proteins (RBPs) play essential roles in coordinating germline gene expression and development in all organisms. Here, we report that loss of ADR-2, a member of the adenosine deaminase acting on RNA family of RBPs and the sole adenosine-to-inosine RNA-editing enzyme in Caenorhabditis elegans, can improve fertility in multiple genetic backgrounds. First, we show that loss of RNA editing by ADR-2 restores normal embryo production to subfertile animals that transgenically express a vitellogenin (yolk protein) fusion to green fluorescent protein. Using this phenotype, a high-throughput screen was designed to identify RBPs that when depleted yield synthetic phenotypes with loss of adr-2. The screen uncovered a genetic interaction between ADR-2 and SQD-1, a member of the heterogeneous nuclear ribonucleoprotein family of RBPs. Microscopy, reproductive assays, and high-throughput sequencing reveal that sqd-1 is essential for the onset of oogenesis and oogenic gene expression in young adult animals and that loss of adr-2 can counteract the effects of loss of sqd-1 on gene expression and rescue the switch from spermatogenesis to oogenesis. Together, these data demonstrate that ADR-2 can contribute to the suppression of fertility and suggest novel roles for both RNA editing–dependent and RNA editing–independent mechanisms in regulating embryogenesis.

Funder

National Institutes of Health

National Institute of General Medical Sciences

National Institute of Child Health and Human Development

National Center for Advancing Translational Sciences

Clinical and Translational Sciences

Indiana University Medical Student Program for Research and Scholarship

NIH Office of Research Infrastructure Programs

Publisher

Oxford University Press (OUP)

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