The human branchpoint-interacting stem-loop sequence and structure regulates U2 snRNA expression, branchpoint recognition, and the transcriptome

During pre-mRNA splicing, the branch helix forms when U2 snRNP engages with introns to initiate spliceosome assembly. The branch helix is mutually exclusive with the U2 snRNA branchpoint-interacting stem loop (BSL). In yeast, BSL alteration affects branchpoint recognition, but its role in human cells, where branchpoint usage is more flexible, is unknown. To examine the impact of perturbing BSL base pairing, we used a self-contained orthogonal splicing system that pairs an engineered U2 snRNA and