Transcription and Splicing Factor TDP-43: Role in Regulation of Gene Expression in Testis.
Transcription and Splicing Factor TDP-43: Role in Regulation of Gene Expression in Testis.
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DOI：
10.1055/s-0037-1599088
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发表时间：
2017-03
影响因子：
2.7
通讯作者：
中科院分区：
文献类型：
--
作者：
TDP-43（TAR DNA binding Protein of 43 kD）是一种具有多种功能的转录因子和RNA结合蛋白。我们在启动子结合蛋白的筛选中从小鼠睾丸中克隆了TDP-43，并表明它具有转录抑制因子的功能。TDP-43通过促进RNA聚合酶II在启动子处的暂停，在精子发生过程中维持精子细胞特异性Acrv 1基因时空表达的精确模式中发挥作用。我们还表明，TDP-43发挥部分作用，防止体细胞表达的Acrv 1基因作为一种绝缘体结合蛋白。自从10年前发现与几种神经退行性疾病的致病联系以来，TDP-43已成为一种与人类健康相关的蛋白质。异常的翻译后修饰、核出口和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异常TDP-43表达。最后，我们未发表的工作表明，TDP-43对精子形成和男性生育力是不可或缺的。本文就TDP-43在男性生殖细胞和生育中的潜在作用作一综述。
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 Finally, our unpublished work shows that TDP-43 is indispensable for sperm formation and male fertility.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.
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影响因子：
4.8
作者：
Lalmansingh, Avin S.;Urekar, Craig J.;Reddi, Prabhakara P.
通讯作者：
Reddi, Prabhakara P.
影响因子：
--
作者：
Ong CT;Corces VG
通讯作者：
Corces VG
影响因子：
8.8
作者：
Manakov SA;Pezic D;Marinov GK;Pastor WA;Sachidanandam R;Aravin AA
通讯作者：
Aravin AA
影响因子：
3.7
作者：
Li W;Jin Y;Prazak L;Hammell M;Dubnau J
通讯作者：
Dubnau J
影响因子：
3.5
作者：
Ash, Peter E. A.;Zhang, Yong-Jie;Link, Christopher D.
通讯作者：
Link, Christopher D.