Using Alu Elements as Polyadenylation Sites: A Case of Retroposon Exaptation

Using Alu Elements as Polyadenylation Sites: A Case of Retroposon Exaptation
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DOI:
10.1093/molbev/msn249
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发表时间:
2009-02-01
影响因子:
10.7
通讯作者:
Gautheret, Daniel
Gautheret, Daniel
中科院分区:
生物学1区
文献类型:
--
作者:
Chen, Chongjian;Ara, Takeshi;Gautheret, Daniel

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在人类基因组中的110万个Alu逆转录子中,约10,000个插入蛋白质编码基因的3'非翻译区(UTR),并且这些逆转录子中的1%(107个事件)作为多聚腺苷酸化位点(PAS)具有活性。引人注目的是,尽管3' UTR中的Alu是正向或反向插入的,但99%的多聚腺苷酸化活性Alu序列是正向的。共有Alu+序列含有可以通过几个点突变产生多聚腺苷酸化信号和增强子的位点。我们发现,多聚腺苷酸化活性的Alu的链的偏见反映了一个根本的差异,在健身的正义和反义Alu的对切割/多聚腺苷酸化活性。与以前的观点相反,Alu插入不一定代表弱的或神秘的PAS;相反,它们通常构成基因中主要或唯一的PAS,增加了Alu外适应的名单。最后,一些基因携带的PAS是内含子的,并产生可能影响基因功能和/或有助于基因重塑的截短转录物。
Of the 1.1 million Alu retroposons in the human genome, about 10,000 are inserted in the 3' untranslated regions (UTR) of protein-coding genes and 1% of these (107 events) are active as polyadenylation sites (PASs). Strikingly, although Alu's in 3' UTR are indifferently inserted in the forward or reverse direction, 99% of polyadenylation-active Alu sequences are forward oriented. Consensus Alu+ sequences contain sites that can give rise to polyadenylation signals and enhancers through a few point mutations. We found that the strand bias of polyadenylation-active Alu's reflects a radical difference in the fitness of sense and antisense Alu's toward cleavage/polyadenylation activity. In contrast to previous beliefs, Alu inserts do not necessarily represent weak or cryptic PASs; instead, they often constitute the major or the unique PAS in a gene, adding to the growing list of Alu exaptations. Finally, some Alu-borne PASs are intronic and produce truncated transcripts that may impact gene function and/or contribute to gene remodeling.