RNA-binding protein ELAVL2 plays post-transcriptional roles in the regulation of spermatogonia proliferation and apoptosis.
Adolescent
Animals
Apoptosis
/ genetics
Cell Proliferation
/ genetics
Cells, Cultured
Child
Child, Preschool
ELAV-Like Protein 2
/ genetics
Humans
Infant
Male
Mice
RNA Processing, Post-Transcriptional
/ genetics
RNA, Messenger
/ genetics
RNA-Binding Proteins
/ genetics
Spermatogonia
/ metabolism
Stem Cells
/ metabolism
Testis
/ metabolism
RNA-binding protein
azoospermia
male infertility
post-transcriptional regulation
spermatogonial stem cells
Journal
Cell proliferation
ISSN: 1365-2184
Titre abrégé: Cell Prolif
Pays: England
ID NLM: 9105195
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
revised:
22
06
2021
received:
24
01
2021
accepted:
24
06
2021
pubmed:
24
7
2021
medline:
29
9
2021
entrez:
23
7
2021
Statut:
ppublish
Résumé
RNA-binding proteins (RBPs) play essential post-transcriptional roles in regulating spermatogonial stem cells (SSCs) maintenance and differentiation. We identified a conserved and SSCs-enriched RBP ELAVL2 from our single-cell sequencing data, but its function and mechanism in SSCs were unclear. Expressions of ELAVL2 during human and mouse testis development were validated. Stable C18-4 and TCam-2 cell lines with overexpression and knockdown of ELAVL2 were established, which were applied to proliferation and apoptosis analysis. RNA immunoprecipitation and sequencing were used to identify ELAVL2 targets, and regulatory functions of ELAVL2 on target mRNAs were studied. Proteins interacting with ELAVL2 in human and mouse testes were identified using immunoprecipitation and mass spectrometric, which were validated by in vivo and in vitro experiments. ELAVL2 was testis-enriched and preferentially expressed in human and mouse SSCs. ELAVL2 was down-regulated in NOA patients. ELAVL2 promoted proliferation and inhibited apoptosis of C18-4 and TCam-2 cell lines via activating ERK and AKT pathways. ELAVL2 associated with mRNAs encoding essential regulators of SSCs proliferation and survival, and promoted their protein expression at post-transcriptional level. ELAVL2 interacted with DAZL in vivo and in vitro in both human and mouse testes. Taken together, these results indicate that ELAVL2 is a conserved SSCs-enriched RBP that down-regulated in NOA, which regulates spermatogonia proliferation and apoptosis by promoting protein expression of targets.
Identifiants
pubmed: 34296486
doi: 10.1111/cpr.13098
pmc: PMC8450129
doi:
Substances chimiques
ELAV-Like Protein 2
0
ELAVL2 protein, human
0
RNA, Messenger
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13098Subventions
Organisme : Key Research and Development Project of Ningxia
ID : 2020BFH02002
Organisme : National Natural Science Foundation of China
ID : 81871215
Organisme : National Natural Science Foundation of China
ID : 81971368
Organisme : National Natural Science Foundation of China
ID : 82001530
Informations de copyright
© 2021 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.
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