How to make the end of a gene, the simple way

Transcription termination of nearly all protein-coding genes in mammals requires 3’ end processing by a multiprotein complex that will cleave and polyadenylate the messenger RNA precursor. Because a variety of enzyme complexes intervene, 3’ end processing was thought to be fundamentally complex and subject to a multitude of regulatory effects. The possibility to select just one out of several polyadenylation sites, in particular, has caused much questioning and speculation. What appear to be separate mechanisms however can be combined into a defined set of rules, allowing for a relatively simple interpretation of 3’ end processing. Ultimately, readiness of the terminal exon splice site determines when a transcript reaches the maturity to select a nearby polyadenylation signal. Transcriptional pausing then acts in concert, extending the timeframe during which the transcription complex is close to polyadenylation sites. Since RNA polymerase pausing is governed by the same type of sequences in bacteria and metazoans, mammalian transcription termination resembles its prokaryote counterpart more than generally thought.Peer reviewe