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小鼠MEX3C652AA在卵巢中的卵母细胞特异性表达及其在调控母体Fos mRNA中的潜在作用。

Oocyte-Specific Expression of Mouse MEX3C652AA in the Ovary and Its Potential Role in Regulating Maternal Fos mRNA.

作者信息

Li Xue, Li Yan, Liu Chunlian, Jin Mulan, Lu Baisong

机构信息

Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina.

Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina General Hospital, Ningxia Medical University, Ningxia, People's Republic of China.

出版信息

Biol Reprod. 2016 May;94(5):115. doi: 10.1095/biolreprod.115.136630. Epub 2016 Apr 6.

Abstract

Currently, the human MEX3C gene is known to encode an RNA-binding protein of 659 amino acid residues. Here we show that the MEX3C gene has alternative splicing forms giving rise to multiple MEX3C variants, and some cells express MEX3C transcripts coding for short MEX3C isoforms but not transcripts for MEX3C(659AA) MEX3C(659AA) functions as an adaptor protein for Exportin 1 (XPO1)-mediated nuclear export since it increases the cytoplasmic distribution of poly(A)(+) RNA and since addition of the nuclear export signal (NES) sequence to a short MEX3C isoform MEX3C(464AA) confers similar cytoplasmic poly(A)(+) RNA accumulation activity as MEX3C(659AA) FOS mRNA is a potential MEX3C target mRNA. One mechanism by which MEX3C(659AA) could regulate FOS mRNA is by promoting its nuclear export. Overexpressing MEX3C(659AA) significantly increased FOS mRNA expression, whereas mutating the NES of MEX3C(659AA) and treating cells with leptomycin B to inhibit XPO1-mediated nuclear export attenuated FOS upregulation. FOS mRNA is unstable in somatic cells but less so in oocytes; how it is stabilized in the oocytes is unknown. Transcripts for the mouse counterpart of human MEX3C(659AA) (MEX3C(652AA)) are specifically expressed in developing oocytes in the ovary, although total Mex3c transcripts are expressed in both granulosa cells and oocytes. The specific expression of this long MEX3C isoform in oocytes and its ability to enhance FOS mRNA nuclear export and stability all suggest that MEX3C(659AA) is an RNA-binding protein that preserves maternal FOS mRNA in oocytes.

摘要

目前已知人类MEX3C基因编码一种由659个氨基酸残基组成的RNA结合蛋白。在此我们表明,MEX3C基因具有可变剪接形式,可产生多种MEX3C变体,并且一些细胞表达编码短MEX3C异构体的MEX3C转录本,但不表达MEX3C(659AA)的转录本。MEX3C(659AA)作为一种衔接蛋白,参与输出蛋白1(XPO1)介导的核输出,因为它增加了聚腺苷酸(poly(A))⁺RNA的细胞质分布,并且向短MEX3C异构体MEX3C(464AA)添加核输出信号(NES)序列可赋予与MEX3C(659AA)相似的细胞质聚腺苷酸(poly(A))⁺RNA积累活性。FOS mRNA是一种潜在的MEX3C靶标mRNA。MEX3C(659AA)调节FOS mRNA的一种机制可能是促进其核输出。过表达MEX3C(659AA)显著增加FOS mRNA表达,而突变MEX3C(659AA)的NES并用地塞米松处理细胞以抑制XPO1介导的核输出会减弱FOS的上调。FOS mRNA在体细胞中不稳定,但在卵母细胞中相对稳定;其在卵母细胞中如何稳定尚不清楚。人类MEX3C(659AA)的小鼠对应物(MEX3C(652AA))的转录本在卵巢发育中的卵母细胞中特异性表达,尽管总Mex3c转录本在颗粒细胞和卵母细胞中均有表达。这种长MEX3C异构体在卵母细胞中的特异性表达及其增强FOS mRNA核输出和稳定性的能力均表明,MEX3C(659AA)是一种在卵母细胞中保存母体FOS mRNA的RNA结合蛋白。

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