The novel function of miR-3195 for mutant PROK2 (c.223-4C>A) degradation.
The novel function of miR-3195 for mutant PROK2 (c.223-4C>A) degradation.
复制标题
miR-3195 对突变体 PROK2 (c.223-4C>A) 降解的新功能。
DOI：
10.1002/cbin.11496
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发表时间：
2021
影响因子：
3.9
通讯作者：
Li Pin
中科院分区：
文献类型：
--
作者：
Zhou Shasha;Li Pin
卡尔曼综合征（KS）是一种罕见的人类遗传性疾病，其特征是低促性腺激素性性腺功能减退，嗅觉功能减退或缺失。多个基因的突变，包括趋化因子prokineticin-2（PROK 2），被认为有助于胚胎期促性腺激素释放激素神经元的异常迁移。然而，KS的不同遗传方式的机制尚未得到全面的确定。在这篇文章中，我们介绍了一个KS患者与他的母亲在PROK 2（c.223 - 4C>A）相同的突变的情况。对他的白细胞进行RNA测序分析，发现了一个新的PROK 2转录本，与他父母的转录本相比，该转录本含有一个部分内含子（192 bp）。此外，我们观察到hsa-miR-3195在他和他父亲的血清中的表达水平低于他母亲的血清。出乎意料的是，hsa-miR-3195也被鉴定为特异性靶向该患者异常PROK 2转录物的192 bp内含子。我们确定hsa-miR-3195的高表达可以在体外有效靶向异常的PROK 2并稳定PROK 2的正常功能，这为患者及其母亲具有相同基因型的不同表型提供了可能的解释。
Kallmann syndrome (KS) is a rare human genetic disorder characterized by hypogonadotropic hypogonadism with the reduction or absence of olfactory sense. Mutations in multiple genes, including chemokine prokineticin‐2 (PROK2), are considered to contribute to the abnormal migration of gonadotropin‐releasing hormone neurons in the embryonic stage. However, the mechanisms of the different inheritance modes of KS have not been comprehensively determined. In this article, we present the case of one KS patient with the same mutation in PROK2 (c.223‐4C>A) as his mother. RNA sequencing analysis of his leukocytes showed a new transcript of PROK2, which contained a partial intron (192 bp) compared to those of his parents. Furthermore, we observed that hsa‐miR‐3195 was expressed at low levels in his and his father's sera compared to his mother's. Unexpectedly, hsa‐miR‐3195 was also identified to specifically target the 192 bp intron of the aberrant PROK2 transcript of this patient. We determined that high expression of hsa‐miR‐3195 could efficiently target aberrant PROK2 and stabilize the normal function of PROK2 in vitro, which provided a probable explanation for the different phenotypes of the patient and his mother with the same genotype.