The RNA-binding protein Adad1 is necessary for germ cell maintenance and meiosis in zebrafish.


Journal

PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074

Informations de publication

Date de publication:
08 2023
Historique:
received: 21 12 2022
accepted: 06 07 2023
revised: 18 08 2023
medline: 21 8 2023
pubmed: 8 8 2023
entrez: 8 8 2023
Statut: epublish

Résumé

The double stranded RNA binding protein Adad1 (adenosine deaminase domain containing 1) is a member of the adenosine deaminase acting on RNAs (Adar) protein family with germ cell-specific expression. In mice, Adad1 is necessary for sperm differentiation, however its function outside of mammals has not been investigated. Here, through an N-ethyl-N-nitrosourea (ENU) based forward genetic screen, we identified an adad1 mutant zebrafish line that develops as sterile males. Further histological examination revealed complete lack of germ cells in adult mutant fish, however germ cells populated the gonad, proliferated, and entered meiosis in larval and juvenile fish. Although meiosis was initiated in adad1 mutant testes, the spermatocytes failed to progress beyond the zygotene stage. Thus, Adad1 is essential for meiosis and germline maintenance in zebrafish. We tested if spermatogonial stem cells were affected using nanos2 RNA FISH and a label retaining cell (LRC) assay, and found that the mutant testes had fewer LRCs and nanos2-expressing cells compared to wild-type siblings, suggesting that failure to maintain the spermatogonial stem cells resulted in germ cell loss by adulthood. To identify potential molecular processes regulated by Adad1, we sequenced bulk mRNA from mutants and wild-type testes and found mis-regulation of genes involved in RNA stability and modification, pointing to a potential broader role in post-transcriptional regulation. Our findings suggest that the RNA regulatory protein Adad1 is required for fertility through regulation of spermatogonial stem cell maintenance in zebrafish.

Identifiants

pubmed: 37552671
doi: 10.1371/journal.pgen.1010589
pii: PGENETICS-D-22-01463
pmc: PMC10437952
doi:

Substances chimiques

Adenosine Deaminase EC 3.5.4.4
RNA 63231-63-0
RNA-Binding Proteins 0
Zebrafish Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1010589

Subventions

Organisme : NICHD NIH HHS
ID : R03 HD097433
Pays : United States
Organisme : NICHD NIH HHS
ID : R15 HD107594
Pays : United States

Informations de copyright

Copyright: © 2023 Islam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Kazi Nazrul Islam (KN)

Biology Department, University of Massachusetts Boston, Boston, Massachusetts, United States of America.

Anuoluwapo Ajao (A)

Biology Department, University of Massachusetts Boston, Boston, Massachusetts, United States of America.

Kavita Venkataramani (K)

Biology Department, University of Massachusetts Boston, Boston, Massachusetts, United States of America.

Joshua Rivera (J)

Biology Department, University of Massachusetts Boston, Boston, Massachusetts, United States of America.
Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, Massachusetts, United States of America.

Shailja Pathania (S)

Biology Department, University of Massachusetts Boston, Boston, Massachusetts, United States of America.
Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, Massachusetts, United States of America.

Katrin Henke (K)

Department of Orthopaedics, Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.

Kellee Renee Siegfried (KR)

Biology Department, University of Massachusetts Boston, Boston, Massachusetts, United States of America.

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Classifications MeSH