Evidence map›Paper›PMID 33077959›Full record

ArticleNature biotechnology2021

RNA timestamps identify the age of single molecules in RNA sequencing.

Samuel G Rodriques, Linlin M Chen, Sophia Liu, Ellen D Zhong, Joseph R Scherrer, Edward S Boyden, Fei Chen

Open access · greenAbstract readLetter
In one paragraph

Article in Nature biotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.8field-weighted citation impact, top 8% of its field
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

37 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Evolution of Engineered ADAR-Based RNA Editing Systems.International journal of molecular sciences · 2026
    Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Emerging clinical applications of ADAR based RNA editing.Stem cells translational medicine · 2025
    Review
  11. Review
  12. Post-Transcriptional Modular Synthetic Receptors.bioRxiv : the preprint server for biology · 2024
    Article
  13. Toward DNA-Based Recording of Biological Processes.International journal of molecular sciences · 2024
    Review
  14. Article
  15. Article
  16. Review
  17. A dynamical perspective: moving towards mechanism in single-cell transcriptomics.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Samuel G Rodriques *Department of Physics, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2509-0861
Linlin M Chen *Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Sophia LiuBiophysics Program, Harvard University, Boston, MA, USA.
Ellen D ZhongComputational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6345-1907
Joseph R ScherrerDepartment of Physics, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-0424-3483
Edward S BoydenDepartment of Media Arts and Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA. edboyden@mit.edu.ORCID http://orcid.org/0000-0002-0419-3351
Fei ChenBroad Institute of Harvard and MIT, Cambridge, MA, USA. chenf@broadinstitute.org.ORCID http://orcid.org/0000-0003-2308-3649
Broad Institute · USMassachusetts Institute of Technology · USHarvard University · USHoward Hughes Medical Institute · US

Funding

MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6M
Center for Genomically Engineered OrgansRM1HG008525 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2015 to 2019
$10.2M
Recording neural activities onto DNAR01MH103910 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI BOYDEN, EDWARD S., CHURCH, GEORGE M · 2013 to 2017
$9.5M
Novel Platforms for Systematic Optical Control of Complex Neural Circuits In VivoR01DA029639 · NIDA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2010 to 2023
$6.7M
Graduate Training in Computational and Systems BiologyT32GM087237 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BURGE, CHRISTOPHER B · 2009 to 2023
$4.6M
Millisecond-Timescale Whole-Brain Neural Activity Mapping in Health and DiseaseDP1NS087724 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2013 to 2017
$3.9M
RNA Scaffolds for Cell Specific Multiplexed Neural ObservationR01MH114031 · NIMH · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2017 to 2020
$2.8M
Characterizing glioma heterogeneity with novel multiplexed nanoscale imaging technologiesDP5OD024583 · OD · BROAD INSTITUTE, INC. · PI CHEN, FEI · 2017 to 2021
$2.2M
Whole-brain recording into nucleic acids using template-independent polymerasesUF1NS107697 · NINDS · NORTHWESTERN UNIVERSITY · PI TYO, KEITH EDWARD JAGGARD · 2018 to 2018
$1.7M
Howard Hughes Medical InstituteNHGRI NIH HHS RM1 HG008525NIDA NIH HHS R01 DA029639NIGMS NIH HHS T32 GM008313NIGMS NIH HHS T32 GM087237NIH HHS DP5 OD024583NIMH NIH HHS R01 MH103910NIMH NIH HHS R01 MH114031NINDS NIH HHS DP1 NS087724NINDS NIH HHS UF1 NS107697
6 · The paper itself

Abstract

Current approaches to single-cell RNA sequencing (RNA-seq) provide only limited information about the dynamics of gene expression. Here we present RNA timestamps, a method for inferring the age of individual RNAs in RNA-seq data by exploiting RNA editing. To introduce timestamps, we tag RNA with a reporter motif consisting of multiple MS2 binding sites that recruit the adenosine deaminase ADAR2 fused to an MS2 capsid protein. ADAR2 binding to tagged RNA causes A-to-I edits to accumulate over time, allowing the age of the RNA to be inferred with hour-scale accuracy. By combining observations of multiple timestamped RNAs driven by the same promoter, we can determine when the promoter was active. We demonstrate that the system can infer the presence and timing of multiple past transcriptional events. Finally, we apply the method to cluster single cells according to the timing of past transcriptional activity. RNA timestamps will allow the incorporation of temporal information into RNA-seq workflows.

Indexed as

3T3 CellsAdenosine DeaminaseAlgorithmsAnimalsCatalytic DomainHEK293 CellsHumansMiceRNARNA-Binding ProteinsRNA EditingSequence Analysis, RNASingle Molecule ImagingTime FactorsADARB1 protein, humanAdenosine DeaminaseRNARNA-Binding Proteins

Identifiers

PMID33077959
PMCPMC7956158
OpenAlexW3093441456

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.