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

TY - JOUR

T1 - Principles for RNA metabolism and alternative transcription initiation within closely spaced promoters

AU - Chen, Yun

AU - Pai, Athma A

AU - Herudek, Jan

AU - Lubas, Michal

AU - Meola, Nicola

AU - Järvelin, Aino I.

AU - Andersson, Robin

AU - Pelechano, Vicent

AU - Steinmetz, Lars M.

AU - Jensen, Torben Heick

AU - Sandelin, Albin Gustav

PY - 2016/9/1

Y1 - 2016/9/1

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 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.

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 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.

KW - Journal Article

U2 - 10.1038/ng.3616

DO - 10.1038/ng.3616

M3 - Journal article

C2 - 27455346

SN - 1061-4036

VL - 48

SP - 984

EP - 994

JO - Nature: New biology

JF - Nature: New biology

IS - 9

ER -