RNA binding protein BOULE forms aggregates in mammalian testis.

RNA binding protein BOULE forms aggregates in mammalian testis.
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RNA结合蛋白Boule在哺乳动物睾丸中形成聚集体。

DOI:
10.7555/jbr.36.20220072
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发表时间:
2022-06-28
影响因子:
2.3
通讯作者:
Xu, Eugene Yujun
Xu, Eugene Yujun
中科院分区:
医学4区
文献类型:
--
作者:
Yujuan, Su;Xinghui, Guo;Min, Zang;Zhengyao, Xie;Tingting, Zhao;Xu, Eugene Yujun

文献摘要

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传统上认为淀粉样蛋白是导致神经退行性变的病理性蛋白质聚集体。然而,新的证据越来越多地表明,非病理性淀粉样蛋白在动物正常发育过程中形成。淀粉样蛋白聚集体的形成最初被认为是动物配子发生的保守特征。这一假设是基于这样的发现,即受调节的淀粉样蛋白形成通过减数分裂特异性RNA结合蛋白来控制酵母减数分裂。另外的支持来自于证明DAZL(哺乳动物配子发生特异性RNA结合蛋白)也在体内形成SDS抗性聚集体的研究。在这里,我们报告的证据聚集BOULE形成,另一个DAZ家族蛋白,在精子发育过程中。数据表明,在小鼠睾丸中,BOULE形成抗SDS的淀粉样聚集体。BOULE聚集体的形成与精子发生过程中的动态发育表达相关,但在BOULE基因敲除的睾丸中消失。我们还映射了必不可少的小区域在体外BOULE聚集,直接下游DAZ重复序列,并发现聚集与温度呈正相关。我们还对来自小鼠睾丸的BOULE聚集体进行了增强的UV交联免疫沉淀,发现聚集体与大量精子发生相关的mRNA结合。这些发现提供了深入了解的配子发生特异性RNA结合蛋白作为一个保守的功能在哺乳动物生殖的淀粉样蛋白的属性。进一步的研究是必要的,以了解在小鼠精子发生过程中BOULE淀粉样蛋白的形成的功能意义。
Amyloids have traditionally been considered pathologic protein aggregates which contribute to neurodegeneration. New evidence however increasingly suggests that non-pathological amyloids are formed in animals during normal development. Amyloid-like aggregate formation was originally thought to be a conserved feature of animal gametogenesis. This hypothesis was based on findings which suggest that regulated amyloid formations govern yeast meiosis by way of meiosis-specific RNA binding proteins. Additional support came from studies which demonstrate that DAZL, a mammalian gametogenesis-specific RNA binding protein, also forms SDS-resistant aggregates in vivo. Here, we report evidence of aggregated BOULE formations, another DAZ family protein, during sperm development. Data suggest that in mouse testis, BOULE forms SDS-resistant amyloid-like aggregates. BOULE aggregate formation correlates with dynamic developmental expression during spermatogenesis but disappeared in Boule knockout testis. We also mapped essential small region in vitro BOULE aggregations, immediately downstream DAZ repeats, and found that aggregations positively correlated with temperature. We also performed enhanced UV cross-linking immunoprecipitation on BOULE aggregates from mouse testes and found that aggregates bind with a large number of spermatogenesis-related mRNAs. These findings provide insight into the amyloidogenic properties of gametogenesis-specific RNA binding proteins as a conserved feature in mammalian reproduction. Further investigation is warranted to understand the functional significance of BOULE amyloid-like formation during mouse spermatogenesis.