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dc.contributor.author
Ball, Christopher B.
dc.contributor.author
Rodriguez, Karina F.
dc.contributor.author
Stumpo, Deborah J.
dc.contributor.author
Ribeiro Neto, Fernando
dc.contributor.author
Korach, Kenneth S.
dc.contributor.author
Blackshear, Perry J.
dc.contributor.author
Birnbaumer, Lutz
dc.contributor.author
Ramos, Silvia B. V.
dc.date.available
2020-01-30T19:20:12Z
dc.date.issued
2014-05
dc.identifier.citation
Ball, Christopher B.; Rodriguez, Karina F.; Stumpo, Deborah J.; Ribeiro Neto, Fernando; Korach, Kenneth S.; et al.; The RNA-binding protein, ZFP36L2, influences ovulation and oocyte maturation; Public Library of Science; Plos One; 9; 5; 5-2014; 1-12
dc.identifier.issn
1932-6203
dc.identifier.uri
http://hdl.handle.net/11336/96256
dc.description.abstract
ZFP36L2 protein destabilizes AU-rich element-containing transcripts and has been implicated in female fertility. In the C57BL/6NTac mouse, a mutation in Zfp36l2 that results in the decreased expression of a form of ZFP36L2 in which the 29 N-terminal amino acid residues have been deleted, ΔN-ZFP36L2, leads to fertilized eggs that arrest at the two-cell stage. Interestingly, homozygous ΔN-Zfp36l2 females in the C57BL/6NTac strain release 40% fewer eggs than the WT littermates (Ramos et al., 2004), suggesting an additional defect in ovulation and/or oocyte maturation. Curiously, the same ΔN-Zfp36l2 mutation into the SV129 strain resulted in anovulation, prompting us to investigate a potential problem in ovulation and oocyte maturation. Remarkably, only 20% of ΔN-Zfp36l2 oocytes in the 129S6/SvEvTac strain matured ex vivo, suggesting a defect on the oocyte meiotic maturation process. Treatment of ΔN-Zfp36l2 oocytes with a PKA inhibitor partially rescued the meiotic arrested oocytes. Furthermore, cAMP levels were increased in ΔN-Zfp36l2 oocytes, linking the cAMP/PKA pathway and ΔN-Zfp36l2 with meiotic arrest. Since ovulation and oocyte maturation are both triggered by LHR signaling, the downstream pathway was investigated. Adenylyl cyclase activity was increased in ΔN-Zfp36l2 ovaries only upon LH stimulation. Moreover, we discovered that ZFP36L2 interacts with the 3′UTR of LHR mRNA and that decreased expression levels of Zfp36l2 correlates with higher levels of LHR mRNA in synchronized ovaries. Furthermore, overexpression of ZFP36L2 decreases the endogenous expression of LHR mRNA in a cell line. Therefore, we propose that lack of the physiological down regulation of LHR mRNA levels by ZFP36L2 in the ovaries is associated with anovulation and oocyte meiotic arrest.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library of Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
ZFP36L2
dc.subject
Oocyte Maturation
dc.subject.classification
Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
The RNA-binding protein, ZFP36L2, influences ovulation and oocyte maturation
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-10-28T18:26:24Z
dc.journal.volume
9
dc.journal.number
5
dc.journal.pagination
1-12
dc.journal.pais
Estados Unidos
dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Ball, Christopher B.. University of North Carolina; Estados Unidos
dc.description.fil
Fil: Rodriguez, Karina F.. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Stumpo, Deborah J.. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Ribeiro Neto, Fernando. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Korach, Kenneth S.. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Blackshear, Perry J.. University of Duke; Estados Unidos. National Institutes of Health; Estados Unidos
dc.description.fil
Fil: Birnbaumer, Lutz. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Ramos, Silvia B. V.. University of North Carolina; Estados Unidos
dc.journal.title
Plos One
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0097324
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pone.0097324
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