|
| 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.
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| Overall design |
eCLIP analysis of FLAG-PTBP1 binding in HEK-293 Flp-In TREx cell lines, with size-matched input control.
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| |
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| Contributor(s) |
Haque N, Kishor A, Hogg JR |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Oct 10, 2019 |
| Last update date |
May 30, 2020 |
| Contact name |
J. Robert Hogg |
| E-mail(s) |
j.hogg@nih.gov
|
| 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 |
| |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
|
| Samples (4)
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| Relations |
| BioProject |
PRJNA576926 |
| SRA |
SRP225117 |
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