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| Status |
Public on Nov 11, 2016 |
| Title |
Modulation of nonsense-mediated decay by rapamycin |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Rapamycin is a naturally occurring macrolide whose target is at the core of nutrient and stress regulation in a wide range of species. Despite well-established roles as an inhibitor of cap-dependent mRNA translation, relatively little is known about its effects on other modes of RNA processing. Here, we characterize the landscape of rapamycin-induced post-transcriptional gene regulation. Transcriptome analysis of rapamycin-treated cells revealed genome-wide changes in alternative mRNA splicing and pronounced changes in NMD-sensitive isoforms. We demonstrate that despite well-documented attenuation of cap-dependent mRNA translation, rapamycin can augment NMD of certain transcripts. Rapamycin-treatment significantly reduces the levels of both endogenous and exogenous PTC-containing mRNA isoforms and its effects are dose-, UPF1- and 4EBP-dependent manner. The PTC-containing SRSF6 transcript exhibits a shorter half-life upon rapamycin-treatment as compared to the non-PTC isoform. Rapamycin-treatment also caused depletion of PTC-containing mRNA isoforms from polyribosomes, underscoring the functional relationship between translation and NMD. Enhanced NMD activity also correlates with an enrichment of the nuclear Cap Binding Complex (CBC) in rapamycin-treated cells. Our data demonstrate that rapamycin modulates global RNA homeostasis by NMD.
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| Overall design |
We performed cytoplasmic RNA-seq of HEK 293 T cells stimulated with rapamycin, emetine or control, in triplicates.
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| |
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| Contributor(s) |
Martinez-Nunez RT, Sanford JR |
| Citation(s) |
27899591 |
| Submission date |
Nov 10, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Andrew Wallace |
| Organization name |
University of California, Santa Cruz
|
| Department |
Molecular, Cell and Developmental Biology
|
| Lab |
Sanford Laboratory
|
| Street address |
University of California, Santa Cruz Molecular, Cell & Developmental Biology Sinsheimer Labs 1156 High Street
|
| City |
Santa Cruz |
| State/province |
CA |
| ZIP/Postal code |
95064 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
|
| Samples (9)
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| Relations |
| BioProject |
PRJNA353126 |
| SRA |
SRP093249 |
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