title: Principles for RNA metabolism and alternative transcription initiation within closely spaced promoters.
abstract: 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.
authors.affiliation: The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.|Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Athma A
authors.initials: AA
authors.lastname: Pai
authors.affiliation: Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Herudek
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.|Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
authors.forename: Michal
authors.initials: M
authors.lastname: Lubas
authors.affiliation: Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
authors.forename: Nicola
authors.initials: N
authors.lastname: Meola
authors.affiliation: European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
authors.forename: Aino I
authors.initials: AI
authors.lastname: Järvelin
authors.affiliation: The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Robin
authors.identifier: 0000-0003-1516-879X
authors.initials: R
authors.lastname: Andersson
authors.affiliation: European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
authors.forename: Vicent
authors.initials: V
authors.lastname: Pelechano
authors.affiliation: European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.|Stanford Genome Technology Center, Palo Alto, California, USA.|Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
authors.affiliation: Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
authors.forename: Torben Heick
authors.initials: TH
authors.lastname: Jensen
authors.affiliation: The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.|Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Albin
authors.identifier: 0000-0002-7109-7378
authors.initials: A
authors.lastname: Sandelin
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008957:Models, Genetic; D026723:Polyadenylation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D012313:RNA