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首页> 外文期刊>Molecular and Cellular Biology >Wobble Splicing Reveals the Role of the Branch Point Sequence-to-NAGNAG Region in 3′ Tandem Splice Site Selection
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Wobble Splicing Reveals the Role of the Branch Point Sequence-to-NAGNAG Region in 3′ Tandem Splice Site Selection

机译:摆动拼接揭示了分支点序列至NAGNAG区在3'串联拼接位点选择中的作用

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Alternative splicing involving the 3′ tandem splice site NAGNAG sequence may play a role in the structure-function diversity of proteins. However, how 3′ tandem splice site utilization is determined is not well understood. We previously demonstrated that 3′ NAGNAG-based wobble splicing occurs mostly in a tissue- and developmental stage-independent manner. Bioinformatic analysis reveals that the nucleotide preceding the AG dinucleotide may influence 3′ splice site utilization; this is also supported by an in vivo splicing assay. Moreover, we found that the intron sequence plays an important role in 3′ splice site selection for NAGNAG wobble splicing. Mutations of the region between the branch site and the NAGNAG 3′ splice site, indeed, affected the ratio of the distal/proximal AG selection. Finally, we found that single nucleotide polymorphisms around the NAGNAG motif could affect the splice site choice, which may lead to a change in mRNA patterns and influence protein function. We conclude that the NAGNAG motif and its upstream region to the branch point sequence are required for 3′ tandem splice site selection.
机译:涉及3'串联剪接位点NAGNAG序列的替代剪接可能在蛋白质的结构功能多样性中起作用。然而,如何确定3'串联拼接位点的利用尚不清楚。先前我们证明了基于3'NAGNAG的摆动拼接主要以组织和发育阶段无关的方式发生。生物信息学分析表明,AG二核苷酸之前的核苷酸可能影响3'剪接位点的利用。体内剪接分析也支持了这一点。此外,我们发现内含子序列在NAGNAG摆动剪接的3'剪接位点选择中起着重要作用。实际上,分支位点和NAGNAG 3'剪接位点之间的区域的突变影响了远端/近端AG选择的比率。最后,我们发现,NANAGG基序周围的单核苷酸多态性可能影响剪接位点的选择,这可能导致mRNA模式的改变并影响蛋白质功能。我们得出结论,对于3'串联剪接位点选择,需要NAGNAG图案及其上游区域到分支点序列。

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