A developmental switch in transcription factor isoforms during spermatogenesis controlled by alternative messenger RNA 3′-end formation

Hang Wang, Becky L. Sartini, Clarke F. Millette, Daniel L. Kilpatrick

Research output: Contribution to journalArticlepeer-review

Abstract

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 that Srebf2_v1 mRNAs 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 that Srebf2_v1 transcripts 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 the Srebf2 gene. 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. The Srebf2 gene thus provides a useful model to explore the role of alternative polyadenylation in regulating stage-dependent functions of important protein regulators in spermatogenic cells.

Original languageEnglish (US)
Pages (from-to)318-323
Number of pages6
JournalBiology of reproduction
Volume75
Issue number3
DOIs
StatePublished - Sep 2006

Keywords

  • Developmental biology
  • Gametogenesis
  • Gene regulation
  • Spermatogenesis
  • Testis

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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