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RRM 结构域而非 hnRNP C1/C2 的 Asp/Glu 结构域,对于 Ron 外显子 11 前体 mRNA 的剪接调控是必需的。

RRM but not the Asp/Glu domain of hnRNP C1/C2 is required for splicing regulation of Ron exon 11 pre-mRNA.

机构信息

School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Korea.

Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, Korea.

出版信息

BMB Rep. 2019 Nov;52(11):641-646. doi: 10.5483/BMBRep.2019.52.11.080.

Abstract

The Ron proto-oncogene is a human receptor for macrophage-stimulating protein (MSP). The exclusion of exon 11 in alternative splicing generates ΔRON protein that is constitutively activated. Heterogenous ribonucleaoprotein (hnRNP) C1/C2 is one of the most abundant proteins in cells. In this manuscript, we showed that both hnRNP C1 and C2 promoted exon 11 inclusion of Ron pre-mRNA and that hnRNP C1 and hnRNP C2 functioned independently but not cooperatively. Moreover, hnRNP C1 stimulated exon 11 splicing through intron 10 activation but not through intron 11 splicing. Furthermore, we showed that, whereas the RRM domain was required for hnRNP C1 function, the Asp/Glu domain was not. In conclusion, hnRNP C1/C2 promoted exon 11 splicing independently by stimulating intron 10 splicing through RRM but not through the Asp/Glu domain. [BMB Reports 2019; 52(11): 641-646].

摘要

Ron 原癌基因是巨噬细胞刺激蛋白(MSP)的人类受体。选择性剪接排除外显子 11 会产生组成性激活的 ΔRON 蛋白。异质核核糖核蛋白(hnRNP)C1/C2 是细胞中最丰富的蛋白质之一。在本文中,我们表明 hnRNP C1 和 C2 均促进 Ron 前体 mRNA 的外显子 11 包含,并且 hnRNP C1 和 hnRNP C2 独立但不协同发挥作用。此外,hnRNP C1 通过激活内含子 10 而不是通过内含子 11 剪接来刺激外显子 11 剪接。此外,我们表明,虽然 RRM 结构域对于 hnRNP C1 的功能是必需的,但 Asp/Glu 结构域不是必需的。总之,hnRNP C1/C2 通过 RRM 刺激内含子 10 剪接而不是通过 Asp/Glu 结构域独立促进外显子 11 剪接。[BMB 报告 2019;52(11):641-646]。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a92/6889891/389c864b9bcf/bmb-52-641f1.jpg

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