TauCstF-64 Mediates Correct mRNA Polyadenylation and Splicing of Activator and Repressor Isoforms of the Cyclic AMP-Responsive Element Modulator (CREM) in Mouse Testis

Spermatogenesis is coordinated by the spatial and temporal expression of many transcriptional and posttranscriptional factors. The cyclic AMP-responsive element modulator (CREM) gene encodes both activator and repressor isoforms that act as transcription factors to regulate spermiogenesis. We found...

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Bibliographic Details
Published in:Biology of reproduction 2016-02, Vol.94 (2), p.34-34
Main Authors: Grozdanov, Petar N, Amatullah, Atia, Graber, Joel H, MacDonald, Clinton C
Format: Article
Language:English
Subjects:
Alternative Splicing
Animals
Cleavage Stimulation Factor - genetics
Cleavage Stimulation Factor - metabolism
Cyclic AMP Response Element Modulator - genetics
Cyclic AMP Response Element Modulator - metabolism
Male
Mice
Polyadenylation
Protein Isoforms - genetics
Protein Isoforms - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Spermatogenesis - physiology
Spermatozoa - metabolism
Testis - metabolism
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Summary:Spermatogenesis is coordinated by the spatial and temporal expression of many transcriptional and posttranscriptional factors. The cyclic AMP-responsive element modulator (CREM) gene encodes both activator and repressor isoforms that act as transcription factors to regulate spermiogenesis. We found that the testis-expressed paralog of CstF-64, tauCstF-64 (gene symbol Cstf2t), is involved in a polyadenylation site choice switch of Crem mRNA and leads to an overall decrease of the Crem mRNAs that are generated from internal promoters in Cstf2t(-/-) mice. More surprisingly, loss of tauCstF-64 also leads to alternative splicing of Crem exon 4, which contains an important activation domain. Thus, testis-specific CREMtau2 isoform protein levels are reduced in Cstf2t(-/-) mice. Consequently, expression of 15 CREM-regulated genes is decreased in testes of Cstf2t(-/-) mice at 25 days postpartum. These effects might further contribute to the infertility phenotype of these animals. This demonstrates that tauCstF-64 is an important stage-specific regulator of Crem mRNA processing that modulates the spatial and temporal expression of downstream stage-specific genes necessary for the proper development of sperm in mice.
ISSN:1529-7268
DOI:10.1095/biolreprod.115.134684