An SF1 affinity model to identify branch point sequences in human introns.

An SF1 affinity model to identify branch point sequences in human introns.
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DOI:
10.1093/nar/gkq1046
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发表时间:
2011-03
影响因子:
14.9
通讯作者:
Frankel AD
Frankel AD
中科院分区:
生物学2区
文献类型:
--
作者:
Pastuszak AW;Joachimiak MP;Blanchette M;Rio DC;Brenner SE;Frankel AD

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剪接因子1(SF 1)与哺乳动物内含子的分支点序列(BPS)结合,并且被认为对于某些但不是全部内含子的剪接是重要的。为了帮助识别BPS,特别是那些依赖于SF 1的BPS,我们生成了一个BPS概况模型,其中通过分支点映射验证的SF 1结合亲和力数据被迭代地并入计算模型中。我们搜索了117499个人类内含子的数据集,以获得高于阈值的SF 1亲和力模型的最佳匹配,并计算了每个内含子位置的匹配数量。在减去背景值后,我们发现87.9%的剩余高评分匹配位于3′-剪接位点的上游区域,在该区域通常发现BPS。由于U2 AF 65识别多聚嘧啶序列(PPT)并与SF 1形成合作RNA复合物,我们将SF 1模型与根据U2 AF 65的高亲和力结合序列计算的PPT模型相结合。结合模型,结合位点位置的限制,准确地确定了SF 1的候选人SF 1依赖性剪接结合的内含子。
Splicing factor 1 (SF1) binds to the branch point sequence (BPS) of mammalian introns and is believed to be important for the splicing of some, but not all, introns. To help identify BPSs, particularly those that depend on SF1, we generated a BPS profile model in which SF1 binding affinity data, validated by branch point mapping, were iteratively incorporated into computational models. We searched a data set of 117 499 human introns for best matches to the SF1 Affinity Model above a threshold, and counted the number of matches at each intronic position. After subtracting a background value, we found that 87.9% of remaining high-scoring matches identified were located in a region upstream of 3′-splice sites where BPSs are typically found. Since U2AF65 recognizes the polypyrimidine tract (PPT) and forms a cooperative RNA complex with SF1, we combined the SF1 model with a PPT model computed from high affinity binding sequences for U2AF65. The combined model, together with binding site location constraints, accurately identified introns bound by SF1 that are candidates for SF1-dependent splicing.
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