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Series GSE46433 Query DataSets for GSE46433
Status Public on Jun 28, 2013
Title Promoter directionality is controlled by U1 snRNP and polyadenylation signals
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Transcription of the mammalian genome is pervasive, but productive transcription outside of protein-coding genes is limited by unknown mechanisms. In particular, although RNA polymerase II (RNAPII) initiates divergently from most active gene promoters, productive elongation occurs primarily in the sense-coding direction. Here we show in mouse embryonic stem cells that asymmetric sequence determinants flanking gene transcription start sites control promoter directionality by regulating promoter-proximal cleavage and polyadenylation. We find that upstream antisense RNAs are cleaved and polyadenylated at poly(A) sites (PASs) shortly after initiation. De novo motif analysis shows PAS signals and U1 small nuclear ribonucleoprotein (snRNP) recognition sites to be the most depleted and enriched sequences, respectively, in the sense direction relative to the upstream antisense direction. These U1 snRNP sites and PAS sites are progressively gained and lost, respectively, at the 5' end of coding genes during vertebrate evolution. Functional disruption of U1 snRNP activity results in a dramatic increase in promoter-proximal cleavage events in the sense direction with slight increases in the antisense direction. These data suggest that a U1-PAS axis characterized by low U1 snRNP recognition and a high density of PASs in the upstream antisense region reinforces promoter directionality by promoting early termination in upstream antisense regions, whereas proximal sense PAS signals are suppressed by U1 snRNP. We propose that the U1-PAS axis limits pervasive transcription throughout the genome.
Overall design 3' end sequencing of poly (A) + RNAs in mouse ES cells with and without U1 snRNP inhibition using antisense morpholino oligonucleotides (AMO). Each with two biological replicates.
Contributor(s) Almada AE, Wu X, Kriz AJ, Burge CB, Sharp PA
Citation(s) 23792564
Submission date Apr 26, 2013
Last update date May 15, 2019
Contact name Xuebing Wu
Phone 2123047615
Organization name Columbia University
Department Medicine/Systems Biology
Lab Xuebing Wu
Street address 630 West 168th Street
City New York
State/province NY
ZIP/Postal code 10032
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (6)
GSM1130096 WT_1
GSM1130097 WT_2
GSM1130098 SCR_1
BioProject PRJNA200323
SRA SRP021541

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Supplementary file Size Download File type/resource
GSE46433_RAW.tar 90.6 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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