• PMID: 8702738
• Gene Name: CREB1
• Condition: Associated with spermatogenesis
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Associated with spermatogenesis

Alternative exon splicing controls a translational switch from activator to repressor isoforms of transcription factor CREB during spermatogenesis

Walker WH, Girardet C, Habener JF.

The cAMP/protein kinase A signaling pathway activates the cAMP-responsive transcription factor CREB. Here we describe a unique alternative RNA splicing event that occurs during the development of germ cells in the testis, resulting in a translational switch from an mRNA encoding activator CREB to an mRNA encoding novel inhibitor CREB isoforms (I-CREBs). Alternative splicing of an additional exon into the CREB mRNA in mid to late pachytene spermatocytes results in the premature termination of translation and consequent downstream reinitiation of translation producing I-CREBs. The I-CREBs down-regulate cAMP-activated gene expression by inhibiting activator CREB from binding to cAMP response elements. Further, the developmental stage-specific expression of I-CREBs in germ cells of the seminiferous tubules correlates with the cyclical down-regulation of activator CREB, suggesting that I-CREBs repress expression of the cAMP-inducible CREB gene as well as other genes transiently induced by cAMP during the 12-day cycle of spermatogenesis. FAU - Walker, W H AU - Walker WH AD - Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02114, USA. FAU - Girardet, C AU - Girardet C