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Nature子刊:中科院上海生科院冯英博狗官方网站发现hnRNPK调控MRPL33剪接在结肠癌的重要功能

摘要 : 2017年9月4日,国际学术权威刊物自然出版集团旗下子刊《Oncogene》杂志上在线发表了中国科学院上海生科院冯英组题为“MRPL33 and its splicing regulator hnRNPK are required for mitochondria function and implicated in tumor progression”最新研究进展。
2017年9月4日,国际学术权威刊物自然出版集团旗下子刊《Oncogenesis》杂志上在线发表了中国科学院上海生科院冯英组题为“MRPL33 and its splicing regulator hnRNPK are required for mitochondria function and implicated in tumor progression”最新研究进展。研究揭示了线粒体核糖体蛋白MRPL33的剪接异构体及剪接调控因子hnRNPK在结直肠癌发生发展中的调控作用。研究生刘丽娜,罗春玲和罗阳君为论文共同第一作者,冯英研究员为论文通讯作者。 MRPL33是一种核糖体大亚基蛋白,与线粒体16S rRNA一起参与线粒体核糖体大亚基组装, MRPL相关家族蛋白在线粒体功能方面具有重要的维护作用,而MRPL33的不同剪接异构体是否具有不同功能目前还不清楚。 博狗官方网站对MRPL33主要的剪接异构体形式进行了功能研究,发现MRPL33-L能够促进多种肿瘤细胞的生长,抑制凋亡,敲出则导致肿瘤细胞线粒体功能受损。MRPL33的剪接受多种剪接因子的调控,其中剪接因子hnRNPK能够结合在可变外显子上调控MRPL33的剪接。该研究进一步表明MRPL33-L和hnRNPK在结直肠癌的形成过程中具有重要的博狗官方网站首页学意义。 原文链接: MRPL33 and its splicing regulator hnRNPK are required for mitochondria function and implicated in tumor progression 原文摘要: MRPL33 gene encodes a large mitoribosomal subunit protein, which may be involved in mitochondrial translation. Although two splice variants of MRPL33 have been described, its splicing regulation remains elusive. Here we observed that inclusion of alternative exon 3 was greatly promoted in a panel of human cancer cells. Depletion of the exon 3-containing long isoform of MRPL33 (MRPL33-L) led to impaired proliferation and increased apoptosis in cancer cell lines and in a xenograft model. MRPL33-L knockdown could also induce mitochondrial dysfunction including increased accumulation of reactive oxygen species, decreased ATP production and 16 S rRNA levels. We further showed that alternative splicing of MRPL33-L pre-mRNA is regulated by hnRNPK and that knocking down hnRNPK could phenocopy MRPL33-L depletion. More importantly, overexpression of MRPL33-L could increase tumorigenic potential of hnRNPK-depleted cancer cells, likely indicating that hnRNPK mediates tumorigenesis through splicing regulation of MRPL33 pre-mRNA. Finally, we found that inclusion of MRPL33 exon 3 was promoted in human colorectal cancer tissues and this was correlated with hnRNPK levels. In summary, our findings underscore the biological significance of MRPL33-L and hnRNPK in the tumor formation and identifies hnRNPK as a critical splicing regulator of MRPL33 pre-mRNA in cancer cells. 来源: Oncogene 浏览次数:0

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