title: TauCstF-64 Mediates Correct mRNA Polyadenylation and Splicing of Activator and Repressor Isoforms of the Cyclic AMP-Responsive Element Modulator (CREM) in Mouse Testis.
abstract: 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.
authors.affiliation: Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas.
authors.forename: Petar N
authors.initials: PN
authors.lastname: Grozdanov
authors.affiliation: Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas.
authors.forename: Atia
authors.initials: A
authors.lastname: Amatullah
authors.affiliation: Center for Genome Dynamics, The Jackson Laboratory, Bar Harbor, Maine.
authors.forename: Joel H
authors.initials: JH
authors.lastname: Graber
authors.affiliation: Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas clint.macdonald@ttuhsc.edu.
authors.forename: Clinton C
authors.initials: CC
authors.lastname: MacDonald
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D039241:Cleavage Stimulation Factor / Q000235:genetics / Q000378:metabolism*; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D026723:Polyadenylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013091:Spermatogenesis / Q000502:physiology; D013094:Spermatozoa / Q000378:metabolism; D013737:Testis / Q000378:metabolism*
chemical_list: D039241:Cleavage Stimulation Factor; C497411:Crem protein, mouse; C492658:Cstf2t protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D051786:Cyclic AMP Response Element Modulator
keywords: CREM; alternative splicing; cleavage and polyadenylation; spermatogenesis; τCstF-64