Genome-wide identification of zero nucleotide recursive splicing in Drosophila.
Genome-wide identification of zero nucleotide recursive splicing in Drosophila.
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DOI：
10.1038/nature14475
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发表时间：
2015-05-21
期刊：
影响因子：
64.8
通讯作者：
Graveley BR
中科院分区：
文献类型：
--
作者：
Duff MO;Olson S;Wei X;Garrett SC;Osman A;Bolisetty M;Plocik A;Celniker SE;Graveley BR
递归剪接是指在剪接后重新产生的5′剪接位点--棘齿点上进行再剪接，从而分多步去除大内含子的过程。递归剪接首先在果蝇超双胸（Ubx）基因中被发现，此后只有三个额外的果蝇基因被实验证明经历递归剪接。在这里，我们确定了197个零核苷酸外显子棘轮点115果蝇基因的130个内含子从发育时间点，解剖组织，培养细胞产生的总RNA测序数据。递归剪接的顺序性质通过鉴定由剪接到棘轮点和从棘轮点剪接产生的lactin内含子来证实。我们还表明，递归剪接是一个组成性的过程中，消耗U2 AF抑制递归剪接，棘轮点的序列和功能是进化保守的果蝇。最后，我们确定了四个递归剪接的人类基因，其中一个也是递归剪接在果蝇。总之，这些结果表明，递归剪接是常用的果蝇，发生在人类，并提供了深入了解的机制，其中一些大的内含子被删除。
Recursive splicing is a process in which large introns are removed in multiple steps by resplicing at ratchet points - 5′ splice sites recreated after splicing. Recursive splicing was first identified in the Drosophila Ultrabithorax (Ubx) gene and only three additional Drosophila genes have since been experimentally shown to undergo recursive splicing. Here, we identify 197 zero nucleotide exon ratchet points in 130 introns of 115 Drosophila genes from total RNA sequencing data generated from developmental time points, dissected tissues, and cultured cells. The sequential nature of recursive splicing was confirmed by identification of lariat introns generated by splicing to and from the ratchet points. We also show that recursive splicing is a constitutive process, that depletion of U2AF inhibits recursive splicing, and that the sequence and function of ratchet points are evolutionarily conserved in Drosophila. Finally, we identified four recursively spliced human genes, one of which is also recursively spliced in Drosophila. Together these results indicate that recursive splicing is commonly used in Drosophila, occurs in human and provides insight into the mechanisms by which some large introns are removed.