Tajnik Mojca, Vigilante Alessandra, Braun Simon, Hänel Heike, Luscombe Nicholas M, Ule Jernej, Zarnack Kathi, König Julian
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy.
UCL Genetics Institute, Department of Genetics, Evolution & Environment, University College London, Gower Street, London WC1E 6BT, UK Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Nucleic Acids Res. 2015 Dec 2;43(21):10492-505. doi: 10.1093/nar/gkv956. Epub 2015 Sep 22.
The 3' untranslated regions (3' UTRs) of transcripts serve as important hubs for posttranscriptional gene expression regulation. Here, we find that the exonisation of intergenic Alu elements introduced new terminal exons and polyadenylation sites during human genome evolution. While Alu exonisation from introns has been described previously, we shed light on a novel mechanism to create alternative 3' UTRs, thereby opening opportunities for differential posttranscriptional regulation. On the mechanistic level, we show that intergenic Alu exonisation can compete both with alternative splicing and polyadenylation in the upstream gene. Notably, the Alu-derived isoforms are often expressed in a tissue-specific manner, and the Alu-derived 3' UTRs can alter mRNA stability. In summary, we demonstrate that intergenic elements can affect processing of preceding genes, and elucidate how intergenic Alu exonisation can contribute to tissue-specific posttranscriptional regulation by expanding the repertoire of 3' UTRs.
转录本的3'非翻译区（3'UTR）是转录后基因表达调控的重要枢纽。在此，我们发现基因间Alu元件的外显子化在人类基因组进化过程中引入了新的末端外显子和多聚腺苷酸化位点。虽然此前已有关于内含子中Alu外显子化的描述，但我们揭示了一种产生可变3'UTR的新机制，从而为差异转录后调控创造了机会。在机制层面，我们表明基因间Alu外显子化可与上游基因的可变剪接和多聚腺苷酸化相互竞争。值得注意的是，Alu衍生的异构体通常以组织特异性方式表达，且Alu衍生的3'UTR可改变mRNA稳定性。总之，我们证明基因间元件可影响上游基因的加工过程，并阐明基因间Alu外显子化如何通过扩展3'UTR库促进组织特异性转录后调控。
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