RT Journal Article SR Electronic T1 Principles for RNA metabolism and alternative transcription initiation within closely spaced promoters JF bioRxiv FD Cold Spring Harbor Laboratory SP 055731 DO 10.1101/055731 A1 Yun Chen A1 Athma A. Pai A1 Jan Herudek A1 Michal Lubas A1 Nicola Meola A1 Aino I. Järvelin A1 Robin Andersson A1 Vicent Pelechano A1 Lars M. Steinmetz A1 Torben Heick Jensen A1 Albin Sandelin YR 2016 UL http://biorxiv.org/content/early/2016/07/13/055731.abstract AB Mammalian transcriptomes are complex and formed by extensive promoter activity. In addition, gene promoters are largely divergent and initiate transcription of reverse-oriented promoter upstream transcripts (PROMPTs). Although PROMPTs are commonly terminated early, influenced by polyadenylation sites, promoters often cluster so that the divergent activity of one might impact another. Here, we find that the distance between promoters strongly correlates with the expression, stability and length of their associated PROMPTs. Adjacent promoters driving divergent mRNA transcription support PROMPT formation, but due to polyadenylation site constraints, these transcripts tend to spread into the neighboring mRNA on the same strand. This mechanism to derive new alternative mRNA transcription start sites (TSSs) is also evident at closely spaced promoters supporting convergent mRNA transcription. We suggest that basic building blocks of divergently transcribed core promoter pairs, in combination with the wealth of TSSs in mammalian genomes, provides a framework with which evolution shapes transcriptomes.