TDP43 depletion rescues aberrant CFTR exon 9 skipping
TDP43 depletion rescues aberrant CFTR exon 9 skipping
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DOI：
10.1016/j.febslet.2006.01.052
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发表时间：
2006-02-01
期刊：
影响因子：
3.5
通讯作者：
Baralle, FE
中科院分区：
文献类型：
--
作者：
Ayala, YM;Pagani, F;Baralle, FE
Cftr外显子9存在3‘剪接点多态，(UG)(M)U-n，其组成影响剪接。TDP43特异性地结合转录本的UG区，并在体外抑制剪接。我们报道，通过RNA干扰耗尽TDP43可以消除不利的(UG)(M)U-n序列引起的剪接抑制，表明TDP43在体内具有强大的抑制作用。我们还表明，UG-TDP43相互作用比其他外显子9剪接调控元件具有主导作用。这些结果表明，剪接位点附近的TDP43关联决定了正剪接调控元件的进化，以对比这种抑制。(C)2006年欧洲生化学会联合会。爱思唯尔出版，版权所有。
CFTR exon 9 presents a 3' splice site polymorphism, (UG)(m)U-n, whose composition influences splicing. TDP43 specifically binds the UG tract of the transcript and inhibits splicing in vitro. We report that depletion of TDP43 through RNA interference removes splicing inhibition caused by unfavorable (UG)(m)U-n sequences, indicating that TDP43 exerts a potent inhibitory effect in vivo. We also show that the UG-TDP43 interaction has a dominant role over other exon 9 splicing regulatory elements. These results suggest that TDP43 association near a splice site has determined the evolution of positive splicing regulatory elements to contrast this inhibition. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.