Special shout-out to first author @GyeungYun_Kim
and co-authors @__ccarroll, @thetruezach, and Mustafa Tuncay

Similarly, in the sea, an upstream boat can prepare the waters so a downstream boat can embark more efficiently—if someone like U1 snRNP shows the way

Our findings support a model in which U1 snRNP favors productive elongation from upstream promoters, triggering downstream promoter activation by destabilizing nucleosomes and promoting promoter escape

A gene-specific U1 snRNP that inhibits a premature polyadenylation site can restore downstream promoter activation

By activating premature polyadenylation sites in transcripts originating from upstream promoters, U1 snRNP inhibition increases RNAPII promoter-proximal pausing and reduces chromatin accessibility at downstream internal promoters

Similarly, premature termination of upstream transcription—before RNA Polymerase II initiated upstream can reach downstream promoters—using the dCas9 system also reduces expression from downstream internal promoters

U1 snRNP inhibition decreases transcription overall, but especially in downstream internal promoters of genes that contain a premature polyadenylation site in between two alternative promoters

We show that downstream internal promoters are often highly active, even though they typically contain weaker promoter-like sequences

Work done by the one and only x.com/steventmick
who was an undergrad at the time (and now a PhD student in our lab!)

Diving into the evolution of their sequences, we found that human hybrid exons with orthologous first exons in other species usually gained 3' splice sites or whole exons upstream, while those with orthologous internal exons often gained promoter elements 5/6

Surprisingly, transcription start sites of hybrid exons are typically centered at the 3' splice site, suggesting tight coupling between splicing and transcription initiation 4/6

We identified more than 80,000 human hybrid first-internal exons. We found they have strong 3' splice sites, and often possess a relaxed chromatin state, allowing transcription initiation within the gene body 3/6

We employed a deep learning pipeline to dissect the sequence features governing the co-regulation of transcription initiation and splicing in hybrid exons-those exons that serve as first or internal exons in different transcripts 2/6