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Alu Exonization Events Reveal Features Required for Precise Recognition of Exons by the Splicing Machinery
 

Summary: Alu Exonization Events Reveal Features Required for
Precise Recognition of Exons by the Splicing Machinery
Schraga Schwartz, Nurit Gal-Mark, Nir Kfir, Ram Oren, Eddo Kim, Gil Ast*
Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
Abstract
Despite decades of research, the question of how the mRNA splicing machinery precisely identifies short exonic islands within
the vast intronic oceans remains to a large extent obscure. In this study, we analyzed Alu exonization events, aiming to
understand the requirements for correct selection of exons. Comparison of exonizing Alus to their non-exonizing counterparts
is informative because Alus in these two groups have retained high sequence similarity but are perceived differently by the
splicing machinery. We identified and characterized numerous features used by the splicing machinery to discriminate
between Alu exons and their non-exonizing counterparts. Of these, the most novel is secondary structure: Alu exons in general
and their 59 splice sites (59ss) in particular are characterized by decreased stability of local secondary structures with respect to
their non-exonizing counterparts. We detected numerous further differences between Alu exons and their non-exonizing
counterparts, among others in terms of exon­intron architecture and strength of splicing signals, enhancers, and silencers.
Support vector machine analysis revealed that these features allow a high level of discrimination (AUC = 0.91) between
exonizing and non-exonizing Alus. Moreover, the computationally derived probabilities of exonization significantly correlated
with the biological inclusion level of the Alu exons, and the model could also be extended to general datasets of constitutive
and alternative exons. This indicates that the features detected and explored in this study provide the basis not only for precise
exon selection but also for the fine-tuned regulation thereof, manifested in cases of alternative splicing.
Citation: Schwartz S, Gal-Mark N, Kfir N, Oren R, Kim E, et al. (2009) Alu Exonization Events Reveal Features Required for Precise Recognition of Exons by the

  

Source: Ast, Gil - Department of Molecular Genetics and Biochemistry, Tel Aviv University

 

Collections: Biology and Medicine