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Semin Reprod Med 2017; 35(02): 167-172
DOI: 10.1055/s-0037-1599088
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Transcription and Splicing Factor TDP-43: Role in Regulation of Gene Expression in Testis

Prabhakara P. Reddi
1   Department of Comparative Biosciences, University of Illinois Urbana Champaign, College of Veterinary Medicine, Urbana, Illinois
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Publication History

Publication Date:
09 March 2017 (online)

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Abstract

TDP-43 (TAR DNA binding Protein of 43 kD) 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-specific Acrv1 gene 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 the Acrv1 gene 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 Finally, our unpublished work shows that TDP-43 is indispensable for sperm formation and male fertility.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.

Keywords

TDP-43 - transcription - spermatogenesis - infertility
 

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