Transcriptional control of alternative splicing along time: Ideas change, experiments remain

Abstract

Evidence on the co-transcriptionality of splicing and on a role for the transcription machinery on splice site selection started to be published before the launching of RNA. However, it was during the last 20 years that initial suspicion and speculation gave room to a profuse body of evidence supporting a radical change of view on the regulatory mechanisms of splicing, originally conceived as a purely post-transcriptional event. Surprisingly, the first evidence for co-transcriptional splicing is still one of the strongest ones, probably because “seeing is believing”: In 1988 Beyer and Osheim performed cytological examination of Drosophila genes caught in active transcription and produced beautiful and compelling EM images revealing that many introns are excised as the mRNA is being synthesized, before RNA polymerase II (RNAPII) reaches the end of the gene.