The Pivotal Roles of TIA Proteins in 5′ Splice-Site Selection of <i>Alu</i> Exons and Across Evolution

Nurit Gal-Mark, Schraga Schwartz, Oren Ram, Eduardo Eyras, Gil Ast

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)


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 (5'ss), even in the presence of a stronger 5'ss downstream. Deletion of this PPT shifted selection to the stronger downstream 5'ss. This enhancing effect depended on the strength of the downstream 5'ss, 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 5'ss. A wide-scale evolutionary analysis of introns across 22 eukaryotes revealed an enrichment in PPTs within similar to 20 nt downstream of the 5'ss. For most metazoans, the strength of the 5'ss inversely correlated with the presence of a downstream PPT, indicative of the functional role of the PPT. Finally, we found that the proteins that mediate this effect, TIA and U1C, and in particular their functional domains, are highly conserved across evolution. Overall, these findings expand our understanding of the role of TIA1/TIAR proteins in enhancing recognition of exons, in general, and Alu exons, in particular.
Original languageEnglish
Article numbere1000717
Number of pages13
JournalPLoS Genetics
Issue number11
Publication statusPublished - Nov 2009
Externally publishedYes


Dive into the research topics of 'The Pivotal Roles of TIA Proteins in 5′ Splice-Site Selection of <i>Alu</i> Exons and Across Evolution'. Together they form a unique fingerprint.

Cite this