Summary: The Pivotal Roles of TIA Proteins in 59 Splice-Site
Selection of Alu Exons and Across Evolution
, Schraga Schwartz1.
, Oren Ram1
, Eduardo Eyras2,3"
*, Gil Ast1"
1 Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel, 2 Computational Genomics, Universitat
Pompeu Fabra, Barcelona, Spain, 3 Catalan Institution for Research and Advanced Studies, Barcelona, Spain
More than 5% of alternatively spliced internal exons in the human genome are derived from Alu elements in a process
termed exonization. Alus are comprised of two homologous arms separated by an internal polypyrimidine tract (PPT). In
most exonizations, splice sites are selected from within the same arm. We hypothesized that the internal PPT may prevent
selection of a splice site further downstream. Here, we demonstrate that this PPT enhanced the selection of an upstream 59
splice site (59ss), even in the presence of a stronger 59ss downstream. Deletion of this PPT shifted selection to the stronger
downstream 59ss. This enhancing effect depended on the strength of the downstream 59ss, on the efficiency of base-pairing
to U1 snRNA, and on the length of the PPT. This effect of the PPT was mediated by the binding of TIA proteins and was
dependent on the distance between the PPT and the upstream 59ss. A wide-scale evolutionary analysis of introns across 22
eukaryotes revealed an enrichment in PPTs within ,20 nt downstream of the 59ss. For most metazoans, the strength of the