ADAD1 and ADAD2, testis-specific adenosine deaminase domain-containing proteins, are required for male fertility

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...

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Autores principales:	Elizabeth Snyder, Lauren Chukrallah, Kelly Seltzer, Leslie Goodwin, Robert E. Braun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f2fb7810e35e412cbe9dbc7b9fe1fa81
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spelling	oai:doaj.org-article:f2fb7810e35e412cbe9dbc7b9fe1fa812021-12-02T15:33:11ZADAD1 and ADAD2, testis-specific adenosine deaminase domain-containing proteins, are required for male fertility10.1038/s41598-020-67834-52045-2322https://doaj.org/article/f2fb7810e35e412cbe9dbc7b9fe1fa812020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-67834-5https://doaj.org/toc/2045-2322Abstract 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.Elizabeth SnyderLauren ChukrallahKelly SeltzerLeslie GoodwinRobert E. BraunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elizabeth Snyder Lauren Chukrallah Kelly Seltzer Leslie Goodwin Robert E. Braun ADAD1 and ADAD2, testis-specific adenosine deaminase domain-containing proteins, are required for male fertility
description	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.
format	article
author	Elizabeth Snyder Lauren Chukrallah Kelly Seltzer Leslie Goodwin Robert E. Braun
author_facet	Elizabeth Snyder Lauren Chukrallah Kelly Seltzer Leslie Goodwin Robert E. Braun
author_sort	Elizabeth Snyder
title	ADAD1 and ADAD2, testis-specific adenosine deaminase domain-containing proteins, are required for male fertility
title_short	ADAD1 and ADAD2, testis-specific adenosine deaminase domain-containing proteins, are required for male fertility
title_full	ADAD1 and ADAD2, testis-specific adenosine deaminase domain-containing proteins, are required for male fertility
title_fullStr	ADAD1 and ADAD2, testis-specific adenosine deaminase domain-containing proteins, are required for male fertility
title_full_unstemmed	ADAD1 and ADAD2, testis-specific adenosine deaminase domain-containing proteins, are required for male fertility
title_sort	adad1 and adad2, testis-specific adenosine deaminase domain-containing proteins, are required for male fertility
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/f2fb7810e35e412cbe9dbc7b9fe1fa81
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ADAD1 and ADAD2, testis-specific adenosine deaminase domain-containing proteins, are required for male fertility

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