Exon-Mediated Activation of Transcription Starts
Name
nihms-1545812.pdf
Description
Accepted version
Size
1.37 MB
Format
Unknown
Checksum (MD5)
a64c839c83c5737bebec4f5e8a749a4c
Author(s)
Fiszbein, Ana
Krick, Keegan S
Begg, Bridget E.
Burge, Christopher B
Date Issued
2019
Journal
Cell
Publisher
Elsevier BV
Version
Author's final manuscript
Abstract
© 2019 Elsevier Inc. The processing of RNA transcripts from mammalian genes occurs in proximity to their transcription. Here, we describe a phenomenon affecting thousands of genes that we call exon-mediated activation of transcription starts (EMATS), in which the splicing of internal exons impacts promoter choice and the expression level of the gene. We observed that evolutionary gain of internal exons is associated with gain of new transcription start sites (TSSs) nearby and increased gene expression. Inhibiting exon splicing reduced transcription from nearby promoters, and creation of new spliced exons activated transcription from cryptic promoters. The strongest effects occurred for weak promoters located proximal and upstream of efficiently spliced exons. Together, our findings support a model in which splicing recruits transcription machinery locally to influence TSS choice and identify exon gain, loss, and regulatory change as major contributors to the evolution of alternative promoters and gene expression in mammals.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.CELL.2019.11.002
