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Series GSE138736 Query DataSets for GSE138736
Status Public on May 28, 2020
Title Activation and inhibition of nonsense-mediated mRNA decay control the abundance of alternative polyadenylation products
Organism Homo sapiens
Experiment type Other
Summary Alternative polyadenylation (APA) produces transcript 3’ untranslated regions (3’UTRs) with distinct sequences, lengths, stability, and functions. We show here that APA products include a class of cryptic nonsense-mediated mRNA decay (NMD) substrates with extended 3’UTRs that gene- or transcript-level analyses of NMD often fail to detect. Transcriptome-wide, the core NMD factor UPF1 preferentially recognizes long 3’UTR products of APA, leading to their systematic downregulation. Further, we find that many APA events consistently observed in multiple tumor types are controlled by NMD. Additionally, PTBP1, previously implicated in direct modulation of co-transcriptional polyA site choice, regulates the balance of short and long 3’UTR isoforms by inhibiting NMD. Our data suggest that PTBP1 binding near polyA sites can drive production of long 3’UTR APA products in the nucleus and/or protect them from decay in the cytoplasm. Together, our findings reveal a widespread role for NMD in shaping the outcomes of APA.
Overall design eCLIP analysis of FLAG-PTBP1 binding in HEK-293 Flp-In TREx cell lines, with size-matched input control.
Contributor(s) Haque N, Kishor A, Hogg JR
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Submission date Oct 10, 2019
Last update date May 30, 2020
Contact name J. Robert Hogg
Organization name National Heart, Lung, and Blood Institute
Department Biochemistry and Biophysics Center
Street address 50 South Drive, Room 2341
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (4)
GSM4118095 PTBP1-eCLIP-1
GSM4118096 PTBP1-eCLIP-2
GSM4118097 PTBP1-SIM-1
BioProject PRJNA576926
SRA SRP225117

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Supplementary file Size Download File type/resource
GSE138736_RAW.tar 21.7 Mb (http)(custom) TAR (of BED)
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Raw data are available in SRA
Processed data provided as supplementary file

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