Evidence map›Paper›PMID 38964322›Full record

ArticleMolecular cell2024

Genome-wide quantification of RNA flow across subcellular compartments reveals determinants of the mammalian transcript life cycle.

Robert Ietswaart, Brendan M Smalec, Albert Xu, Karine Choquet, Erik McShane, Ziad Mohamoud Jowhar, Chantal K Guegler, Autum R Baxter-Koenigs, Emma R West, Becky Xu Hua Fu and 3 more

Abstract read
In one paragraph

Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

66 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Robert IetswaartDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: robert.ietswaart@cellforma.com.
Brendan M SmalecDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Albert XuDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
Karine ChoquetDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Erik McShaneDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Ziad Mohamoud JowharDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
Chantal K GueglerDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Autum R Baxter-KoenigsDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Emma R WestDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Becky Xu Hua FuArc Institute, Palo Alto, CA 94305, USA.
Luke GilbertArc Institute, Palo Alto, CA 94305, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Urology, University of California, San Francisco, San Francisco, CA 94518, USA.
Stephen N FloorDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: stephen@floorlab.org.
L Stirling ChurchmanDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: churchman@genetics.med.harvard.edu.

Funding

TRAINING GRANT IN GENETICST32GM007748 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Anne O'Donnell-Luria, Louise Wilkins-Haug · 1985 to 2026
$12.0M
Mechanisms of Transcriptional Control Revealed by Nascent Transcript SequencingR01HG007173 · NHGRI · HARVARD MEDICAL SCHOOL · PI Lee Stirling Churchman · 2013 to 2026
$6.7M
Investigating sex differences in DDX3X mouse modelsR01NS120667 · NINDS · DUKE UNIVERSITY · PI SILVER, DEBRA L. · 2021 to 2025
$3.4M
Direct sequencing of nascent RNA to uncover the functional impact of genetic variants on RNA processingR21HG011682 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCHMAN, LEE STIRLING · 2021 to 2021
$455k
Investigating the role of DDX3 in regulating RNA structure and mRNA exportF30HD110250 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI XU, ALBERT Y · 2022 to 2025
$187k
National Science Foundation DGE-1745303NHGRI NIH HHS R01 HG007173NHGRI NIH HHS R21 HG011682NICHD NIH HHS F30 HD110250NIGMS NIH HHS T32 GM007748NINDS NIH HHS R01 NS120667
6 · The paper itself

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.

Indexed as

Cell NucleusChromatinDEAD-box RNA HelicasesRNA, MessengerActive Transport, Cell NucleusAnimalsCytoplasmExosomesHumansMachine LearningMicePolyribosomesRNA-Binding ProteinsRNA StabilityChromatinDEAD-box RNA HelicasesRNA-Binding ProteinsRNA, MessengerDDX3Xkinetic modelingnuclear exportnuclear RNA degradationpoly(A) tailsRNA-binding proteinsRNA dynamicsRNA flowsubcellular TimeLapse-seqtranslation

Identifiers

PMID38964322
PMCPMC11315470

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.