Transcription and Splicing Factor TDP-43: Role in Regulation of Gene Expression in Testis
| Autor: | Prabhakara P. Reddi |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
Somatic cell Endocrinology Diabetes and Metabolism RNA polymerase II Biology Article 030207 dermatology & venereal diseases 03 medical and health sciences Splicing factor 0302 clinical medicine Endocrinology Transcription (biology) Physiology (medical) Testis mental disorders Animals Humans Spermatogenesis Transcription factor Infertility Male Genetics Regulation of gene expression Gene Expression Regulation Developmental nutritional and metabolic diseases Obstetrics and Gynecology Sperm nervous system diseases DNA-Binding Proteins Fertility Reproductive Medicine biology.protein Signal transduction 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Semin Reprod Med |
| ISSN: | 1526-4564 1526-8004 |
| Popis: | 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 Finally, our unpublished work shows that TDP-43 is indispensable for sperm formation and male fertility.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. |
| Databáze: | OpenAIRE |
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