TY - JOUR T1 - Principles for RNA metabolism and alternative transcription initiation within closely spaced promoters JF - bioRxiv DO - 10.1101/055731 SP - 055731 AU - Yun Chen AU - Athma A. Pai AU - Jan Herudek AU - Michal Lubas AU - Nicola Meola AU - Aino I. Järvelin AU - Robin Andersson AU - Vicent Pelechano AU - Lars M. Steinmetz AU - Torben Heick Jensen AU - Albin Sandelin Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/05/27/055731.abstract N2 - 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. ER -