Document Type

Article

Publication Date

7-14-2020

Keywords

JMG, JAXCC

JAX Source

Sci Rep 2020 Jul 14; 10(1):11536

PMID

32665638

DOI

https://doi.org/10.1038/s41598-020-67834-5

Grant

HD072627,HD083521,RR033367

Abstract

Adenosine-to-inosine RNA editing, a fundamental RNA modification, is regulated by adenosine deaminase (AD) domain containing proteins. Within the testis, RNA editing is catalyzed by ADARB1 and is regulated in a cell-type dependent manner. This study examined the role of two testis-specific AD domain proteins, ADAD1 and ADAD2, on testis RNA editing and male germ cell differentiation. ADAD1, previously shown to localize to round spermatids, and ADAD2 had distinct localization patterns with ADAD2 expressed predominantly in mid- to late-pachytene spermatocytes suggesting a role for both in meiotic and post-meiotic germ cell RNA editing. AD domain analysis showed the AD domain of both ADADs was likely catalytically inactive, similar to known negative regulators of RNA editing. To assess the impact of Adad mutation on male germ cell RNA editing, CRISPR-induced alleles of each were generated in mouse. Mutation of either Adad resulted in complete male sterility with Adad1 mutants displaying severe teratospermia and Adad2 mutant germ cells unable to progress beyond round spermatid. However, mutation of neither Adad1 nor Adad2 impacted RNA editing efficiency or site selection. Taken together, these results demonstrate ADAD1 and ADAD2 are essential regulators of male germ cell differentiation with molecular functions unrelated to A-to-I RNA editing.

Comments

The authors would like to sincerely thank The Jackson Laboratory for their support in generating mutant models and members of the Braun Laboratory (Alexandra Lyahkovich) and the Snyder Laboratory (Gabriella Acoury) for their assistance with molecular analysis.

This article is licensed under a Creative Commons Attribution 4.0 International License.

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