Summary: Intronic Alus Influence Alternative Splicing
, Oren Ram1.
, Eddo Kim1.
, Noa Sela1.
, Amir Goren1
, Erez Y. Levanon2
, Gil Ast1
1 Department of Human Molecular Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, 2 Department of Genetics, Harvard Medical School, Boston,
Massachusetts, United States of America
Examination of the human transcriptome reveals higher levels of RNA editing than in any other organism tested to date.
This is indicative of extensive double-stranded RNA (dsRNA) formation within the human transcriptome. Most of the editing
sites are located in the primate-specific retrotransposed element called Alu. A large fraction of Alus are found in intronic
sequences, implying extensive Alu-Alu dsRNA formation in mRNA precursors. Yet, the effect of these intronic Alus on splicing
of the flanking exons is largely unknown. Here, we show that more Alus flank alternatively spliced exons than constitutively
spliced ones; this is especially notable for those exons that have changed their mode of splicing from constitutive to
alternative during human evolution. This implies that Alu insertions may change the mode of splicing of the flanking exons.
Indeed, we demonstrate experimentally that two Alu elements that were inserted into an intron in opposite orientation