A developmental switch in transcription factor isoforms during spermatogenesis controlled by alternative messenger RNA 3'-end formation
Department of Physiology
Alternative Splicing; Animals; Blotting, Northern; Cricetinae; Humans; Male; Meiosis; Mice; RNA; RNA 3' End Processing; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Spermatogenesis; Sterol Regulatory Element Binding Protein 2; Sterol Regulatory Element Binding Proteins; Testis
Cellular and Molecular Physiology | Life Sciences | Medicine and Health Sciences
Spermatogenic cells elaborate a highly specialized differentiation program that is mediated in part by germ cell-enriched transcription factors. This includes a novel member of the sterol response element-binding factor family, SREBF2_v1/SREBP2gc. Somatic SREBFs are predominantly synthesized as precursor proteins and are critical regulators of cholesterol and fatty acid synthesis. In contrast, SREBF2_v1 bypasses the precursor pathway and has been directly implicated in spermatogenic cell-specific gene expression. During spermatogenesis, SREBF2 precursor transcripts predominate in premeiotic stages, while SREBF2_v1 is highly upregulated specifically in pachytene spermatocytes and round spermatids. In the present study, we demonstrate thatSrebf2_v1mRNAs are present in the testis of several mammalian species, including humans. The basis for the stage-dependent transition in SREBF2 isoforms was also investigated. A 3' rapid amplification of cDNA ends (RACE)-PCR analysis of the rat and human revealed thatSrebf2_v1transcripts are generated by alternative pre-mRNA cleavage/polyadenylation. This involves the use of an intronic, A(A/U)UAAA-independent poly(A) signal within intron 7 of theSrebf2gene. Developmentally regulated competition between germ cell factors that control RNA splicing and pre-mRNA cleavage/polyadenylation may underlie this process. These results define an important role for alternative polyadenylation in male germ cell gene expression and development by controlling a stage-dependent switch in transcription factor structure and function during spermatogenesis. TheSrebf2gene thus provides a useful model to explore the role of alternative polyadenylation in regulating stage-dependent functions of important protein regulators in spermatogenic cells.
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Citation: Biol Reprod. 2006 Sep;75(3):318-23. Epub 2006 May 24. Link to article on publisher's site