HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 75/3/318    most recent biolreprod.106.052209v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, H. Articles by Kilpatrick, D. L. Search for Related Content PubMed PubMed Citation Articles by Wang, H. Articles by Kilpatrick, D. L. Agricola Articles by Wang, H. Articles by Kilpatrick, D. L.

A Developmental Switch in Transcription Factor Isoforms During Spermatogenesis Controlled by Alternative Messenger RNA 3'-End Formation¹

Department of Molecular and Cellular Physiology,³ University of Massachusetts Medical School, Worcester, Massachusetts 01655 Department of Cell Biology, School of Medicine,⁴ University of South Carolina, Columbia, South Carolina 29208

ABSTRACT

Spermatogeniccells 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.

developmental biology, gametogenesis, gene regulation, spermatogenesis, testis

¹ Supported by Public Service grant R01 HD045723.

² Correspondence. FAX: 508 856 5997; daniel.kilpatrick{at}umassmed.edu

This article has been cited by other articles:

				B. L. Sartini, H. Wang, W. Wang, C. F. Millette, and D. L. Kilpatrick Pre-Messenger RNA Cleavage Factor I (CFIm): Potential Role in Alternative Polyadenylation During Spermatogenesis Biol Reprod, March 1, 2008; 78(3): 472 - 482. [Abstract] [Full Text] [PDF]