title: Transcription and Splicing Factor TDP-43: Role in Regulation of Gene Expression in Testis.
abstract: TDP-43 (TARDNA bindingProtein of43kD) is a transcription factor and RNA-binding protein with diverse functions. We cloned TDP-43 from the mouse testis in a screen for promoter-binding proteins and showed that it functions as a transcriptional repressor. TDP-43 plays a role in maintaining the precise pattern of spatiotemporal expression of the spermatid-specificAcrv1gene during spermatogenesis by facilitating RNA polymerase II pausing at the promoter. We also showed that TDP-43 plays a partial role in preventing somatic cell expression of theAcrv1gene by acting as an insulator-binding protein. Since the discovery of a causative link to several neurodegenerative diseases 10 years ago, TDP-43 has emerged as a protein of major human health relevance. Aberrant posttranslational modifications, nuclear exit, and cytoplasmic aggregate formation contribute to loss of neuronal function in patients. Interestingly, aberrant TDP-43 expression has also been reported in the testis and sperm of infertile men. Finally, our unpublished work shows that TDP-43 is indispensable for sperm formation and male fertility. The potential role of TDP-43 in male germ cells and fertility is discussed in this review.
authors.affiliation: Department of Comparative Biosciences, University of Illinois Urbana Champaign, College of Veterinary Medicine, Urbana, Illinois.
authors.forename: Prabhakara P
authors.initials: PP
authors.lastname: Reddi
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005298:Fertility; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D015398:Signal Transduction; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C000598624:TARDBP protein, human