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| Status |
Public on Jul 14, 2020 |
| Title |
RNA-seq of Bafilomycin-treated cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Nonsense-mediated decay (NMD) is a pathway that degrades messenger RNAs containing premature termination codons. Here, a genome-wide screen for NMD factors uncovered an unexpected mechanism that broadly governs 3ʹ untranslated region (UTR)-directed regulation. The screen revealed that NMD requires lysosomal acidification, which allows transferrin-mediated iron uptake, which in turn is necessary for iron-sulfur (Fe-S) cluster biogenesis. This pathway converges on the Fe-S cluster-containing ribosome recycling factor ABCE1, whose impaired function results in the movement of ribosomes into 3ʹ UTRs where they displace exon junction complexes, thereby abrogating NMD. Importantly, these effects extend beyond NMD substrates, with ABCE1 activity required to maintain the accessibility of 3ʹ UTRs to diverse regulators, including microRNAs and RNA binding proteins. Due to the sensitivity of the Fe-S cluster of ABCE1 to iron availability and reactive oxygen species, these findings reveal an unanticipated vulnerability of 3ʹ UTR-directed regulation to lysosomal dysfunction, iron deficiency, and oxidative stress.
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| Overall design |
Method: RNA-seq was performed in HCT116 NMD reporter cells that were either treated with DMSO or 5 nM bafilomycin for 48 hours. Two replicates in each condition, and thus 4 biological samples were used for these experiments.
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| |
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| Contributor(s) |
Zhu X, Zhang H, Mendell JT |
| Citation(s) |
32668236 |
| |
| Submission date |
May 13, 2020 |
| Last update date |
Jul 17, 2020 |
| Contact name |
Joshua Mendell |
| E-mail(s) |
joshua.mendell@utsouthwestern.edu
|
| Organization name |
UT Southwestern Medical Center
|
| Department |
Molecular Biology
|
| Street address |
6000 Harry Hines Blvd., NA6.200A
|
| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390-9148 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE144165 |
Ribosome recycling by ABCE1 links lysosomal function and iron homeostasis to 3ʹ UTR- directed regulation and nonsense-mediated decay |
|
| Relations |
| BioProject |
PRJNA632634 |
| SRA |
SRP261510 |
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