Revisiting the window of opportunity for co-transcriptional splicing efficiency and fidelity

Recently, we reported that changes in transcription elongation rate affect the efficiency and fidelity of precursor mRNA (pre-mRNA) splicing, especially of ribosomal protein (RP) transcripts. Here, we analyse these results in more detail, finding that the majority of RP transcripts with non-consensus 5’ splice sites have reduced splicing efficiency with faster transcription elongation, and improved efficiency with slower elongation, as might be predicted by the “window of opportunity” model for co-transcriptional splicing. In contrast, both faster and slower elongation reduce splicing fidelity, often for the same splicing events, and both faster and slower transcription increase fidelity with a different set of splicing events. We propose that certain non-consensus 5’ splice sites in ribosomal protein transcripts confer a stronger effect of transcription elongation rate on splicing efficiency, possibly by causing a rate-limiting step that delays activation of spliceosomes. The effects of different rates of transcription elongation on splicing fidelity are more difficult to explain by a simple window of opportunity model. We discuss these new findings in the context of current models of co-transcriptional splicing and splicing fidelity.