Explaining the degradation of pervasively transcribed RNAs

Together with Torben Heicks and Lars Steinmetz group, we have shown what makes pervasively transcribed RNAs sensitive to exosomal degradation - publsihed in Nature Structural and Molecular Biology. This is actually the first paper where we use CAGE data from our laboratory(!). Yun Chen and Jette Bornholdt-Lange from the Sandein lab are shared second authors. Here is a summary of this and the related paper in Nature from the Sharp group.

Abstract:

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.