The Dynamics of Cytoplasmic mRNA Metabolism
Open accessPublished version of a preprint
Abstract
For all but a few mRNAs, the dynamics of metabolism are unknown. Here, we developed an experimental and analytical framework for examining these dynamics for mRNAs from thousands of genes. mRNAs of mouse fibroblasts exit the nucleus with diverse intragenic and intergenic poly(A)-tail lengths. Once in the cytoplasm, they have a broad (1000-fold) range of deadenylation rate constants, which correspond to cytoplasmic lifetimes. Indeed, with few exceptions, degradation appears to occur primarily through deadenylation-linked mechanisms, with little contribution from either endonucleolytic cleavage or deadenylation-independent decapping. Most mRNA molecules degrade only after their tail lengths fall below 25 nt. Decay rate constants of short-tailed mRNAs vary broadly (1000-fold) and are larger for short-tailed mRNAs that have previously undergone more rapid deadenylation. This coupling helps clear rapidly deadenylated mRNAs, enabling the large range in deadenylation rate constants to impart a similarly large range in stabilities.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Matplotlib: a 2D graphics environment
Hunter, J. D. (2007) · Computing in Science & Engineering · doi:10.1109/mcse.2007.55 · Cited by 39,249 · see citing works
Wickham, H., Averick, M., Bryan, J., Chang, W., McGowan, L., François, R., Grolemund, G., Hayes, A., Henry, L., Hester, J., et al. (2019) · Journal of Open Source Software · doi:10.21105/joss.01686 · Cited by 22,138 · see citing works
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · see citing works
Python for scientific computing
Oliphant, T. E. (2007) · Computing in Science & Engineering · doi:10.1109/mcse.2007.58 · Cited by 3,303 · see citing works
AU-rich elements: characterization and importance in mRNA degradation
Chen, C.-Y. A., & Shyu, A.-B. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89102-1 · Cited by 1,948 · see citing works
Towards a molecular understanding of microRNA-mediated gene silencing
Jonas, S., & Izaurralde, E. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3965 · Cited by 1,872 · see citing works
Codon Optimality Is a Major Determinant of mRNA Stability
Presnyak, V., Alhusaini, N., Chen, Y.-H., Martin, S., Morris, N., Kline, N., Olson, S., Weinberg, D., Baker, K. E., Graveley, B. R., et al. (2015) · Cell · doi:10.1016/j.cell.2015.02.029 · Cited by 1,078 · see citing works
Human Pumilio Proteins Recruit Multiple Deadenylases to Efficiently Repress Messenger RNAs
Van Etten, J., Schagat, T. L., Hrit, J., Weidmann, C. A., Brumbaugh, J., Coon, J. J., & Goldstrohm, A. C. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.373522 · Cited by 205 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The genetic and biochemical determinants of mRNA degradation rates in mammals
Agarwal, V., & Kelley, D. R. (2022) · Genome Biology · doi:10.1186/s13059-022-02811-x · Cited by 155 · see citing works
Recognition of Poly(A) RNA through Its Intrinsic Helical Structure
Tang, T. T. L., & Passmore, L. A. (2019) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2019.84.039818 · Cited by 29 · see citing works
- Authors
- Eisen, T. J., Eichhorn, S. W., Subtelny, A. O., Lin, K. S., McGeary, S. E., Gupta, S., & Bartel, D. P.
- Affiliations
- Howard Hughes Medical Institute (US)
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Bartel, David P.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 77
- Issue
- 4
- Pages
- 786-799.e10
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC7265681
- OpenAlex
- W2996988556
- Cited by
- 177
- References
- 8
- Citations by year
- 2026: 21 · 2025: 34 · 2024: 33 · 2023: 24 · 2022: 30 · 2021: 20 · 2020: 13 · 2019: 2
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- National Science Foundation
- National Institutes of Health
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- mRNA metabolism, mRNA degradation, poly(A) tail length, deadenylation, mRNA stability, cytoplasmic mRNA, mouse fibroblasts, decay constants, endonucleolytic cleavage, decapping
- MeSH terms
- Animals, Cytoplasm, RNA, Messenger, 3T3 Cells, RNA Stability, Mice, RNA Isoforms
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
