Evidence map›Paper›PMID 33979654›Full record

ArticleCell2021

Dynamic imaging of nascent RNA reveals general principles of transcription dynamics and stochastic splice site selection.

Yihan Wan, Dimitrios G Anastasakis, Joseph Rodriguez, Murali Palangat, Prabhakar Gudla, George Zaki, Mayank Tandon, Gianluca Pegoraro, Carson C Chow, Markus Hafner and 1 more

Abstract read
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.

0numbers the graph read from it
0cells of the map it votes in
117citing 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

117 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Invariant nonequilibrium dynamics in gene regulation optimize information flow.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Detection of a sequence feature for recursive splicing.bioRxiv : the preprint server for biology · 2026
    Article
  11. Article
  12. Article
  13. The Kinetic Intron Hypothesis.bioRxiv : the preprint server for biology · 2026
    Article
  14. Article
  15. Article
  16. Visualizing DNA repair factor recruitment at sites of transcription in single cells.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2026
    Article
  17. Review
  18. The "cutting edge" of non-canonical RNA splicing.Frontiers in molecular biosciences · 2026
    Review
  19. What makes genes burst.Trends in cell biology · 2026
    Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Yihan WanCenter for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Dimitrios G AnastasakisNational Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.
Joseph RodriguezNIEHS, Durham, NC, USA.
Murali PalangatCenter for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Prabhakar GudlaCenter for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
George ZakiBiomedical Informatics and Data Science Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Mayank TandonCenter for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Gianluca PegoraroCenter for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Carson C ChowLaboratory of Biological Modeling, NIDDK, Bethesda, MD, USA.
Markus HafnerNational Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA. Electronic address: markus.hafner@nih.gov.
Daniel R LarsonCenter for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: dan.larson@nih.gov.

Funding

Transcription Dynamics in Single CellsZIABC011383 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LARSON, DANIEL · 2011 to 2025
$23.8M
HiTIF Microscopy Core FacilityZICBC011567 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PEGORARO, GIANLUCA · 2014 to 2025
$15.8M
Environmental regulation of estrogen responsive genes in single living cellsZIAES103331 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI RODRIGUEZ, JOSEPH · 2019 to 2025
$13.0M
LRBGE Optical Microscopy CoreZICBC011574 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KARPOVA, TATIANA · 2014 to 2025
$7.4M
Modeling gene transcriptionZIADK075069 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI CHOW, CARSON · 2012 to 2025
$2.9M
Intramural NIH HHS Z99 CA999999Intramural NIH HHS ZIA BC011383
6 · The paper itself

Abstract

The activities of RNA polymerase and the spliceosome are responsible for the heterogeneity in the abundance and isoform composition of mRNA in human cells. However, the dynamics of these megadalton enzymatic complexes working in concert on endogenous genes have not been described. Here, we establish a quasi-genome-scale platform for observing synthesis and processing kinetics of single nascent RNA molecules in real time. We find that all observed genes show transcriptional bursting. We also observe large kinetic variation in intron removal for single introns in single cells, which is inconsistent with deterministic splice site selection. Transcriptome-wide footprinting of the U2AF complex, nascent RNA profiling, long-read sequencing, and lariat sequencing further reveal widespread stochastic recursive splicing within introns. We propose and validate a unified theoretical model to explain the general features of transcription and pervasive stochastic splice site selection.

Indexed as

Transcription, GeneticExonsHumansIntronsRNA, MessengerRNA PrecursorsRNA Splice SitesRNA SplicingSpliceosomesTranscriptomeRNA, MessengerRNA PrecursorsRNA Splice SitesfluorescenceheterogeneityimagingRNAsingle moleculespliceosomesplicingstochastictranscription

Identifiers

PMID33979654
PMCPMC8183334

What OpenQuestion holds

Textmetadata
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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.