Minimal conditions for exonization of intronic sequences: 5′ splice site formation in Alu exons

Rotem Sorek, Galit Lev-Maor, Mika Reznik, Tal Dagan, Frida Belinky, Dan Graur, Gil Ast*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Alu exonization, which is an evolutionary pathway that creates primate-specific transcriptomic diversity, is a powerful tool for studying alternative-splicing regulation. Through bioinformatic analyses combined with experimental methodology, we identified the mutational changes needed to create functional 5′ splice sites in Alu. We revealed a complex mechanism by which the sequence composition of the 5′ splice site and its base pairing with the small nuclear RNA U1 govern alternative splicing. We show that in Alu-derived GC introns the strength of the base pairing between U1 snRNA and the 5′ splice site controls the skipping/inclusion ratio of alternative splicing. Based on these findings, we identified 7810 Alus within the human genome that are prone to exonization. Mutations in these Alus may cause genetic disorders or contribute to human-specific protein diversity.

Original languageEnglish
Pages (from-to)221-231
Number of pages11
JournalMolecular Cell
Volume14
Issue number2
DOIs
StatePublished - 23 Apr 2004

Funding

FundersFunder number
Chief Scientist of Israel Health Ministry
FD Hope, Israel Cancer Association
Israel Science Foundation
Tel Aviv University

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