Principles for RNA metabolism and alternative transcription initiation within closely spaced promote
Our latest article by Yun Chen et al - published in Nature genetics at http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3616.html
This is a collaboration with Torben Heick-Jensen's lab (and other groups), and explores the underlying rules of promoters, initiation of transcription and RNA decay. In particular, we ask what happens once gene transcription start sites occur closely to each other.
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.
Yun Chen, Athma A Pai, Jan Herudek, Michal Lubas, Nicola Meola, Aino I Jarvelin, RobinAndersson, Vicent Pelechano, Lars M Steinmetz, Torben Heick Jensen, Albin Sandelin.
Also available as preprint here: doi: http://dx.doi.org/10.1101/055731