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| Status |
Public on Jun 22, 2023 |
| Title |
Genome-wide quantification of RNA flow across subcellular compartments reveals determinants of the transcript life cycle |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Series of regulatory mechanisms control eukaryotic mRNAs, from their production on chromatin to their eventual degradation. Dissecting these pathways requires quantitative measurements of mRNA flow across the cell. We developed subcellular TimeLapse-seq to measure the rates at which RNAs are released from chromatin, exported from the nucleus, loaded onto polysomes, and degraded within the nucleus and the cytoplasm. All rates displayed substantial variability genome-wide, and transcripts from genes with related functions flowed across subcellular compartments with similar kinetics. For some genes, most transcripts were rapidly degraded within the nucleus, while the remaining molecules were exported and persisted with stable lifespans. With compartment-specific measurements of poly(A) tail lengths, we found that relationships between tail length and stability differ across the cell. The targets of RNA binding proteins experience distinct RNA flow kinetics, and we found that two, DDX3X and PABPC4, act by controlling the nuclear export of their targets. Finally, we developed a machine learning model to propose additional molecular features that underlie the diverse life cycle of mammalian mRNAs.
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| Overall design |
Subcellular direct RNA sequencing in human K562 cells.
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| Contributor(s) |
Smalec BM, Ietswaart R, Choquet K, McShane E, West ER, Churchman LS |
| Citation missing |
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| Submission date |
Jul 14, 2022 |
| Last update date |
Jun 25, 2023 |
| Contact name |
Karine Choquet |
| E-mail(s) |
karine.choquet@usherbrooke.ca
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| Organization name |
Université de Sherbrooke
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| Department |
Biochemistry and Functional Genomics
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| Street address |
3201 rue Jean-Mignault
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| City |
Sherbrooke |
| State/province |
Québec |
| ZIP/Postal code |
J1E 4K8 |
| Country |
Canada |
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| Platforms (1) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA858812 |
| SRA |
SRP386439 |
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