Nucleic Acids Research Advance Access published online on September 8, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp729
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Evidence for large diversity in the human transcriptome created by Alu RNA editing
1The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel, 2Department of Genetics, Harvard Medical School, Boston, MA 02115, USA, 3Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel Aviv 69978 and 4Cancer Research Center and Institute of Hematology, The Chaim Sheba Medical Center and Tel Aviv University, Tel Aviv 52621, Israel
*To whom correspondence should be addressed. Tel: +972 3 531 7990; Fax: +972 3 736 2560; Email: mehrra{at}mail.biu.ac.il Correspondence may also be addressed to George M. Church. Tel: +1 617 432 5742; Fax: +1 617 432 6513; Email: gmc{at}harvard.edu
Received April 7, 2009. Revised July 9, 2009. Accepted August 18, 2009.
Adenosine-to-inosine (A-to-I) RNA editing alters the original genomic content of the human transcriptome and is essential for maintenance of normal life in mammals. A-to-I editing in Alu repeats is abundant in the human genome, with many thousands of expressed Alu sequences undergoing editing. Little is known so far about the contribution of Alu editing to transcriptome complexity. Transcripts derived from a single edited Alu sequence can be edited in multiple sites, and thus could theoretically generate a large number of different transcripts. Here we explored whether the combinatorial potential nature of edited Alu sequences is actually fulfilled in the human transcriptome. We analyzed datasets of editing sites and performed an analysis of a detailed transcript set of one edited Alu sequence. We found that editing appears at many more sites than detected by earlier genomic screens. To a large extent, editing of different sites within the same transcript is only weakly correlated. Thus, rather than finding a few versions of each transcript, a large number of edited variants arise, resulting in immense transcript diversity that eclipses alternative splicing as mechanism of transcriptome diversity, although with less impact on the proteome.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.