A spliceosomal intron binding protein, IBP160, links position-dependent assembly of intron-encoded box C/D snoRNP to pre-mRNA splicing
A spliceosomal intron binding protein, IBP160, links position-dependent assembly of intron-encoded box C/D snoRNP to pre-mRNA splicing
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DOI：
10.1016/j.molcel.2006.07.011
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发表时间：
2006-09-01
期刊：
影响因子：
16
通讯作者：
Steitz, Joan A.
中科院分区：
文献类型：
--
作者：
Hirose, Tetsuro;Ideue, Takashi;Steitz, Joan A.
脊椎动物中的前-mRNA剪接在分子上与其他过程有关。我们以前报道过，剪接是高效组装内含子编码盒C/D小核仁核糖核蛋白(SnoRNP)所必需的。在剪接体C1复合体中，如果snoRNP蛋白位于内含子分支点上游约50nT处，则snoRNP蛋白可有效地组装成snoRNA序列。在这里，我们确定了负责耦合snoRNP组装和内含子切除的剪接因子。内含子结合蛋白(IBP)160是先前在剪接体C1复合体中检测到的一种解旋酶样蛋白，它以不依赖于序列的方式与前-mRNA结合，与内含子分支位点上游的33-40核苷酸联系，无论是否存在snoRNA。在体外，耗尽IBP160会取消snoRNP的组装。IBP160直接与距离内含子分支位置太近的snoRNA结合会干扰snoRNP的组装。因此，IBP160是将snoRNP生物发生和其他剪接后事件与前mRNA剪接联系起来的关键因素。
Pre-mRNA splicing in vertebrates is molecularly linked to other processes. We previously reported that splicing is required for efficient assembly of intron-encoded box C/D small nucleolar ribonucleoprotein (snoRNP). In the spliceosomal C1 complex, snoRNP proteins efficiently assemble onto snoRNA sequences if they are located about 50 nt upstream of the intron branchpoint. Here, we identify the splicing factor responsible for coupling snoRNP assembly to intron excision. Intron binding protein (IBP) 160, a helicase-like protein previously detected in the spliceosomal C1 complex, binds the pre-mRNA in a sequence-independent manner, contacting nucleotides 33-40 upstream of the intron branch site, regardless of whether a snoRNA is present. Depletion of IBP160 abrogates snoRNP assembly in vitro. IBP160 binding directly to a snoRNA located too close to the intron branch site interferes with snoRNP assembly. Thus, IBP160 is the key factor linking snoRNP biogenesis and perhaps other postsplicing events to pre-mRNA splicing.