Open AccessTranscription and Splicing Factor TDP-43: Role in Regulation of Gene Expression in Testis
Author(s) -
Prabhakara P. Reddi
Publication year - 2017
Publication title -
seminars in reproductive medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.67
H-Index - 81
eISSN - 1526-8004
pISSN - 1526-4564
DOI - 10.1055/s-0037-1599088
Subject(s) - biology , spermatid , rna binding protein , transcription factor , gene , rna splicing , gene expression , repressor , somatic cell , microbiology and biotechnology , transcription (linguistics) , splicing factor , alternative splicing , genetics , messenger rna , rna , sperm , linguistics , philosophy
TDP-43 ( T AR D NA binding P rotein 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 Finally, our unpublished work shows that TDP-43 is indispensable for sperm formation and male fertility.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.