Fig. 7. Simplified hypothesized model of the differential regulation of IR events in IR-1 and IR-2 clusters.

The RBP proteins (such as PRPF39, LUC7L3, LUC7L, TIA1, and RBM25) form a complex that interacts with U1snRNP (not shown) at weak 5′ splice site (5′ ss) to facilitate intron removal. In IR-1, this RBP complex binds the 5′ ss of its own introns in a feedforward loop leading to intron removal and export of mature intron-less mRNAs to the cytoplasm where they are translated to RBP proteins. The RBP complex also removes introns from transcripts that encode oncogenes that are translated to functional onco-proteins. In IR-2, introns in the transcripts of these RBPs are retained in the mature mRNA, leading to accumulation of these intron-containing transcripts in the nucleus, causing reduced translation of these transcripts and thus a reduced level of RBP complexes in the nucleus. Lower levels of functional RBP complexes would reduce translation of these transcripts to functional onco-proteins. Created with Biorender.