近日，日本一個(gè)研究小組日前發(fā)布研究成果說(shuō),，具有腫瘤抑制作用的乳腺癌易感基因BRCA1除可通過(guò)修復(fù)染色體異常來(lái)遏制乳腺癌和卵巢癌外,，還能通過(guò)生成小核糖核酸來(lái)遏制癌癥,。這一成果可協(xié)助研究人員開(kāi)發(fā)出新治療藥物,。
乳腺癌易感基因BRCA1是近年來(lái)發(fā)現(xiàn)的一個(gè)腫瘤抑制基因,，它的結(jié)構(gòu)和功能變化與家族型乳腺癌和卵巢癌的發(fā)生有關(guān)。研究證實(shí),，BRCA1基因發(fā)生突變的人在40歲以前得乳腺癌的概率高達(dá)19%,。
日本大阪大學(xué)特聘副教授河合伸治率領(lǐng)的研究小組在美國(guó)《細(xì)胞生物學(xué)期刊》The Journal of Cell Biology發(fā)表報(bào)告說(shuō)，他們調(diào)查人類(lèi)細(xì)胞中與抑制癌癥有關(guān)的4種小核糖核酸的量時(shí)發(fā)現(xiàn),，如果加強(qiáng)細(xì)胞中BRCA1基因的作用,，這些小核糖核酸的量會(huì)增加，而如果抑制這一基因的作用,，這些小核糖核酸的量則減少,。顯示兩者具密切關(guān)系。
河合伸治說(shuō)：“很多癌癥中都發(fā)現(xiàn)了小核糖核酸的異常,。這些異常有可能與BRCA1基因有關(guān),，這一發(fā)現(xiàn)有可能協(xié)助研究人員開(kāi)發(fā)出新的治療藥物。”
（生物谷Bioon.com）
doi:10.1083/jcb.201110008
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BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex
Shinji Kawai1 and Atsuo Amano2
MicroRNAs (miRNAs) are noncoding RNAs that function as key posttranscriptional regulators of gene expression. miRNA maturation is controlled by the DROSHA microprocessor complex. However, the detailed mechanism of miRNA biogenesis remains unclear. We show that the tumor suppressor breast cancer 1 (BRCA1) accelerates the processing of miRNA primary transcripts. BRCA1 increased the expressions of both precursor and mature forms of let-7a-1, miR-16-1, miR-145, and miR-34a. In addition, this tumor suppressor was shown to be directly associated with DROSHA and DDX5 of the DROSHA microprocessor complex, and it interacted with Smad3, p53, and DHX9 RNA helicase. We also found that BRCA1 recognizes the RNA secondary structure and directly binds with primary transcripts of miRNAs via a DNA-binding domain. Together, these results suggest that BRCA1 regulates miRNA biogenesis via the DROSHA microprocessor complex and Smad3/p53/DHX9. Our findings also indicate novel functions of BRCA1 in miRNA biogenesis, which may be linked to its tumor suppressor mechanism and maintenance of genomic stability.
