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Principles for RNA metabolism and alternative transcription initiation within closely spaced promoters

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  • Yun Chen, Københavns Universitet
  • ,
  • Athma A. Pai, Massachusetts Institute of Technology
  • ,
  • Jan Herudek
  • ,
  • Michal Lubas, Københavns Universitet
  • ,
  • Nicola Meola
  • ,
  • Aino I. Järvelin, University of Oxford, Oxford
  • ,
  • Robin Andersson, Københavns Universitet
  • ,
  • Vicent Pelechano, Karolinska University Hospital, Stockholm
  • ,
  • Lars M. Steinmetz, Stanford University
  • ,
  • Torben Heick Jensen
  • Albin Sandelin, Københavns Universitet

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 found 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 owing 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, provide a framework with which evolution shapes transcriptomes.

TidsskriftNature Genetics
Sider (fra-til)984-994
Antal sider11
StatusUdgivet - 1 sep. 2016

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