2012年3月17日,，北京生命科學(xué)研究所李夏璐研究小組在《FEBS Letters》雜志在線發(fā)表文章,，報(bào)道了癌癥抑制因子RBM5與剪接因子DHX15直接相互作用，從而提高了DHX15核酸解旋酶的活性,。
在肺癌等多種癌癥發(fā)生早期,，都伴隨有染色體3p21.3區(qū)域的缺失，RBM5基因則位于這段區(qū)域內(nèi),。前期研究發(fā)現(xiàn),，RBM5的高表達(dá)能促進(jìn)細(xì)胞凋亡，低表達(dá)則誘導(dǎo)細(xì)胞癌化,。因此,，RBM5一直以來(lái)被認(rèn)為是癌癥抑制相關(guān)因子。最近的兩項(xiàng)研究表明,，該蛋白在調(diào)節(jié)凋亡相關(guān)因子的選擇性剪接中發(fā)揮作用,。然而，對(duì)于RBM5在剪接調(diào)控中的作用機(jī)理仍了解甚少,。
本文首先通過免疫共沉淀的方法,，發(fā)現(xiàn)了兩個(gè)重要的剪接體組份：PRP19和DHX15是RBM5的兩個(gè)新的核內(nèi)結(jié)合蛋白。進(jìn)一步體外實(shí)驗(yàn)證實(shí),，RBM5與這兩個(gè)剪接因子之間存在著直接的相互作用并能有效促進(jìn)DHX15的解旋酶活性,。解旋酶直接參與動(dòng)態(tài)調(diào)控剪接復(fù)合體成熟過程中發(fā)生的一系列RNA：蛋白和RNA：RNA相互作用。這項(xiàng)工作提示了RBM5參與剪接調(diào)控的可能作用機(jī)理,，為RBM5的生物學(xué)功能研究提供了新的線索和依據(jù),。（生物谷 bioon.com）
doi:10.1016/j.febslet.2012.02.052
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Tumor suppressor RBM5 directly interacts with the DExD/H-box protein DHX15 and stimulates its helicase activity
Zhaoyang Niua, Wenxing Jinb, Libo Zhang, Xialu Li
RNA binding motif protein 5 (RBM5) is a candidate tumor suppressor gene. Recent studies showed that RBM5 functions as an alternative splicing regulator of apoptosis-related genes. Here, we identify DHX15 and PRP19, two spliceosome components, as novel RBM5-interacting partners. We then show that the G-patch domain of RBM5 is indispensable for its ability to interact with DHX15. Strikingly, we find that RBM5 stimulates the helicase activity of DHX15 in a G patch domain-dependent manner in vitro. Helicase activities play critical roles in modulating pre-mRNA splicing. Our findings thus suggest a new mechanism underlying the regulatory roles of RBM5 in pre-mRNA splicing.
