Role of Pseudoexons and Pseudointrons in Human Cancer
Figure 1
ATM pseudoexon activated in cancer. (a) Scheme of the ATM pseudoexon insertion caused by a 4 nt deletion (GUAA) occurring 1873 nt downstream from the donor splice site of ATM exon 20. The solid lines indicate introns. Dotted lines include the 65 nt-ATM pseudoexon (gray box). The intron-splicing processing element (ISPE) complementary to U1 snRNA, the RNA component of the U1 small nuclear ribonucleoprotein (snRNP), is underlined. (b) Schematic model of U1snRNP mediated inhibition of pseudoexon insertion in normal conditions. In this model, U1snRNP binding to the ISPE blocks pseudoexon inclusion by inhibiting recruitment of U2snRNP to the 3′splice site region and SRSF1 binding to the stem loop of the pseudoexon (shown as dotted lines). (c) In the case of the disease associated ATM ΔGUAA deletion, the internal U1snRNP binding site is no longer present due to the deletion of the ISPE. This leads to a more efficient binding of SRSF1 to the enhancer site and stabilization of the U2snRNP interaction with the branch site and U1snRNP with the 5′gc donor site.
