Reddi Prabhakara P
Department of Comparative Biosciences, University of Illinois Urbana Champaign, College of Veterinary Medicine, Urbana, Illinois.
Semin Reprod Med. 2017 Mar;35(2):167-172. doi: 10.1055/s-0037-1599088. Epub 2017 Mar 9.
TDP-43 (AR NA binding rotein of 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 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 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 Finally, our unpublished work shows that TDP-43 is indispensable for sperm formation and male fertility.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.
TDP - 43（43kD的AR NA结合蛋白）是一种具有多种功能的转录因子和RNA结合蛋白。我们在筛选启动子结合蛋白的过程中从小鼠睾丸中克隆出TDP - 43，并表明它作为转录抑制因子发挥作用。在精子发生过程中，TDP - 43通过促进RNA聚合酶II在启动子处暂停，在维持精子特异性基因精确的时空表达模式中发挥作用。我们还表明，TDP - 43作为绝缘子结合蛋白，在阻止该基因在体细胞中表达方面发挥部分作用。自10年前发现与几种神经退行性疾病存在因果联系以来，TDP - 43已成为与人类健康密切相关的一种蛋白质。异常的翻译后修饰、核输出和细胞质聚集体形成导致患者神经元功能丧失。有趣的是，在不育男性的睾丸和精子中也报道了TDP - 43的异常表达。最后，我们未发表的研究表明，TDP - 43对精子形成和男性生育能力不可或缺。本文综述了TDP - 43在雄性生殖细胞和生育能力中的潜在作用。
