Polyadenylation site–induced decay of upstream transcripts enforces promoter directionality

Ntini E, Järvelin AI, Bornholdt J, Chen Y, Boyd M, Jørgensen M, Andersson R, Hoof I, Schein A, Andersen PR, Andersen PK, Preker P, Valen E, Zhao X, Pelechano V, Steinmetz LM, Sandelin A, Jensen TH

Nat Struct Mol Biol 20 (8) 923-928 [2013-08-00; online 2013-07-14]

Active human promoters produce promoter-upstream transcripts (PROMPTs). Why these RNAs are coupled to decay, whereas their neighboring promoter-downstream mRNAs are not, is unknown. Here high-throughput sequencing demonstrates that PROMPTs generally initiate in the antisense direction closely upstream of the transcription start sites (TSSs) of their associated genes. PROMPT TSSs share features with mRNA-producing TSSs, including stalled RNA polymerase II (RNAPII) and the production of small TSS-associated RNAs. Notably, motif analyses around PROMPT 3' ends reveal polyadenylation (pA)-like signals. Mutagenesis studies demonstrate that PROMPT pA signals are functional but linked to RNA degradation. Moreover, pA signals are under-represented in promoter-downstream versus promoter-upstream regions, thus allowing for more efficient RNAPII progress in the sense direction from gene promoters. We conclude that asymmetric sequence distribution around human gene promoters serves to provide a directional RNA output from an otherwise bidirectional transcription process.

Vicent Pelechano

PubMed 23851456

DOI 10.1038/nsmb.2640

Crossref 10.1038/nsmb.2640

Publications 7.1.2