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Genome-wide quantification of RNA flow across subcellular compartments reveals determinants of the mammalian transcript life cycle.
- Source :
-
Molecular cell [Mol Cell] 2024 Jul 25; Vol. 84 (14), pp. 2765-2784.e16. Date of Electronic Publication: 2024 Jul 03. - Publication Year :
- 2024
-
Abstract
- Dissecting the regulatory mechanisms controlling mammalian transcripts from production to degradation 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 cytoplasm in human and mouse cells. These rates varied substantially, yet transcripts from genes with related functions or targeted by the same transcription factors and RNA-binding proteins flowed across subcellular compartments with similar kinetics. Verifying these associations uncovered a link between DDX3X and nuclear export. For hundreds of RNA metabolism genes, most transcripts with retained introns were degraded by the nuclear exosome, while the remaining molecules were exported with stable cytoplasmic lifespans. Transcripts residing on chromatin for longer had extended poly(A) tails, whereas the reverse was observed for cytoplasmic mRNAs. Finally, machine learning identified molecular features that predicted the diverse life cycles of mRNAs.<br />Competing Interests: Declaration of interests R.I. is a founder, board member, and/or shareholder of Cellforma, unrelated to the present work.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Humans
Mice
Cytoplasm metabolism
Cytoplasm genetics
RNA Stability
Active Transport, Cell Nucleus
Polyribosomes metabolism
Polyribosomes genetics
Machine Learning
RNA-Binding Proteins metabolism
RNA-Binding Proteins genetics
Exosomes metabolism
Exosomes genetics
RNA, Messenger metabolism
RNA, Messenger genetics
Cell Nucleus metabolism
Cell Nucleus genetics
DEAD-box RNA Helicases metabolism
DEAD-box RNA Helicases genetics
Chromatin metabolism
Chromatin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 84
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 38964322
- Full Text :
- https://doi.org/10.1016/j.molcel.2024.06.008