Evidence that an IRES within the Notch2 coding region can direct expression of a nuclear form of the protein

We previously reported the isolation from a thymic tumor of a feline leukemia virus that had transduced a fragment of the Notch2 gene. Here we present evidence that a nuclear form of Notch2 corresponding to the biologically active intracellular domain (N2ICD) is expressed from this recombinant retrovirus through internal ribosome entry. Internal ribosome entry sites (IRESs) are RNA structural motifs that allow 5' cap-independent recruitment of ribosomal subunits to mRNAs. The Notch2 IRES maps exclusively to Notch2 sequences that correspond to the coding region of the cellular gene. Therefore, these studies not only provide insights into aberrant Notch2 expression in tumors, but they may also inform our understanding of N2ICD generation in the cellular context.