ADAD1 is required for normal translation of nuclear pore and transport protein transcripts in spermatids of Mus musculus†.
LINC complex
RNA-binding proteins
manchette
microtubules
nuclear pore complex
protein transport
spermatids
spermiogenesis
translation regulation
Journal
Biology of reproduction
ISSN: 1529-7268
Titre abrégé: Biol Reprod
Pays: United States
ID NLM: 0207224
Informations de publication
Date de publication:
12 09 2023
12 09 2023
Historique:
received:
28
11
2022
revised:
23
03
2023
accepted:
29
06
2023
pmc-release:
03
07
2024
medline:
18
9
2023
pubmed:
3
7
2023
entrez:
3
7
2023
Statut:
ppublish
Résumé
ADAD1 is a testis-specific RNA-binding protein expressed in post-meiotic spermatids whose loss leads to defective sperm and male infertility. However, the drivers of the Adad1 phenotype remain unclear. Morphological and functional analysis of Adad1 mutant sperm showed defective DNA compaction, abnormal head shaping, and reduced motility. Mutant testes demonstrated minimal transcriptome changes; however, ribosome association of many transcripts was reduced, suggesting ADAD1 may be required for their translational activation. Further, immunofluorescence of proteins encoded by select transcripts showed delayed protein accumulation. Additional analyses demonstrated impaired subcellular localization of multiple proteins, suggesting protein transport is also abnormal in Adad1 mutants. To clarify the mechanism giving rise to this, the manchette, a protein transport microtubule network, and the LINC (linker of nucleoskeleton and cytoskeleton) complex, which connects the manchette to the nuclear lamin, were assessed across spermatid development. Proteins of both displayed delayed translation and/or localization in mutant spermatids implicating ADAD1 in their regulation, even in the absence of altered ribosome association. Finally, ADAD1's impact on the NPC (nuclear pore complex), a regulator of both the manchette and the LINC complex, was examined. Reduced ribosome association of NPC encoding transcripts and reduced NPC protein abundance along with abnormal localization in Adad1 mutants confirmed ADAD1's impact on translation is required for a NPC in post-meiotic germ cells. Together, these studies lead to a model whereby ADAD1's influence on nuclear transport leads to deregulation of the LINC complex and the manchette, ultimately generating the range of physiological defects observed in the Adad1 phenotype.
Identifiants
pubmed: 37399121
pii: 7218337
doi: 10.1093/biolre/ioad069
pmc: PMC10502568
doi:
Substances chimiques
Carrier Proteins
0
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
340-355Subventions
Organisme : NICHD NIH HHS
ID : F32 HD072628
Pays : United States
Organisme : NICHD NIH HHS
ID : K99 HD083521
Pays : United States
Organisme : NICHD NIH HHS
ID : R00 HD083521
Pays : United States
Organisme : NICHD NIH HHS
ID : R03 HD108418
Pays : United States
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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