TY - JOUR
T1 - Minimal conditions for exonization of intronic sequences
T2 - 5′ splice site formation in Alu exons
AU - Sorek, Rotem
AU - Lev-Maor, Galit
AU - Reznik, Mika
AU - Dagan, Tal
AU - Belinky, Frida
AU - Graur, Dan
AU - Ast, Gil
N1 - Funding Information:
We thank M. Kupiec for critical reading, we thank Alan Weiner for the U1 gene, and we thank Adrian Krainer and Stefan Stemm for the SR plasmids. We also thank the Bioinformatics Unit at Tel Aviv University for providing technical assistance and computation facilities, and we thank Amir Goren for generating the website. R.S., G.L.-M., M.R., and G.A. were supported by a grant from the Israel Science Foundation, FD Hope, Israel Cancer Association, Chief Scientist of Israel Health Ministry, and the MOP India-Israel. R.S., T.D., F.B., and D.G. were supported by the Norman and Rose Lederer Chair of Biology at Tel Aviv University.
PY - 2004/4/23
Y1 - 2004/4/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=1942534661&partnerID=8YFLogxK
U2 - 10.1016/S1097-2765(04)00181-9
DO - 10.1016/S1097-2765(04)00181-9
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AN - SCOPUS:1942534661
SN - 1097-2765
VL - 14
SP - 221
EP - 231
JO - Molecular Cell
JF - Molecular Cell
IS - 2
ER -