近日,，來自英國癌癥研究中心倫敦研究所的Jesper Q. Svejstrup等人做了一項關于能夠整合轉錄延伸與mRNA剪接的功能因子的研究，結果發(fā)現了一種新的蛋白復合體DBIRD,。相關論文在3月25日《自然》在線發(fā)表,。
哺乳動物有限的基因卻可以實現極其復雜的蛋白質組，選擇性mRNA剪接是主要的原因,。
剪接在空間和功能上都與轉錄相偶聯,，并被轉錄延伸效率所影響。當pre-mRNA從RNA聚合酶II(RNAPII）合成出來以后,，通過裝配形成信使核糖核蛋白(mRNP)顆粒,，這是pre-mRNA的功能形式，也決定了成熟轉錄物的命運,。
然而,，能夠聯系mRNP顆粒與轉錄酶，并且整合轉錄延伸與mRNA剪接的功能因子還不明確,。因此,，研究人員描繪了人類染色體有關的mRNP顆粒的相互作用組。
這促使了研究人員去鑒定在肺癌1(DBC1)和ZNF326（與核mRNPs及DBC1相互作用的鋅指蛋白）中缺失的蛋白,，結果發(fā)現了一個新奇的蛋白復合物--DBIRD,，它可以直接結合到RNAPII。
DBIRD主要調節(jié)嵌入在富含（A + T）DNA中外顯子的選擇性剪接,，并出現在受到影響的外顯子中,。RNA干擾介導的DBIRD的損耗，導致了DBIRD在轉錄延伸尤其是包含受影響的外顯子區(qū)域里出現區(qū)域特異性減少,。
總的來說,，這些結果表明：DBIRD復合物作為mRNP顆粒和RNAPII的一個連接體，整合了選擇性剪接的調節(jié)與轉錄延伸,。（生物谷Deepblue編譯）
doi: 10.1038/nature10925
PMC:
PMID:
DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation
Pierre Close,Philip East, A. Barbara Dirac-Svejstrup, Holger Hartmann, Mark Heron, Sarah Maslen, Alain Chariot, Johannes S ding, Mark Skehe & Jesper Q. Svejstrup.
Alternative messenger RNA splicing is the main reason that vast mammalian proteomic complexity can be achieved with a limited number of genes.Splicing is physically and functionally coupled to transcription, and is greatly affected by the rate of transcript elongation. As the nascent pre-mRNA emerges from transcribing RNA polymerase II (RNAPII), it is assembled into a messenger ribonucleoprotein (mRNP) particle; this is the functional form of the nascent pre-mRNA and determines the fate of the mature transcript.However, factors that connect the transcribing polymerase with the mRNP particle and help to integrate transcript elongation with mRNA splicing remain unclear. Here we characterize the human interactome of chromatin-associated mRNP particles.This led us to identify deleted in breast cancer 1 (DBC1) and ZNF326 (which we call ZNF-protein interacting with nuclear mRNPs and DBC1 (ZIRD)) as subunits of a novel protein complex—named DBIRD—that binds directly to RNAPII.DBIRD regulates alternative splicing of a large set of exons embedded in (A + T)-rich DNA, and is present at the affected exons. RNA-interference-mediated DBIRD depletion results in region-specific decreases in transcript elongation, particularly across areas encompassing affected exons.Together, these data indicate that the DBIRD complex acts at the interface between mRNP particles and RNAPII, integrating transcript elongation with the regulation of alternative splicing.
