Evidence map›Paper›PMID 31085639›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

Imaging-based pooled CRISPR screening reveals regulators of lncRNA localization.

Chong Wang, Tian Lu, George Emanuel, Hazen P Babcock, Xiaowei Zhuang

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
4.9field-weighted citation impact, top 3% 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

73 citing papers in PubMed, 116 citations in OpenAlex.

  1. Article
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  8. Functional Neurogenomics to Dissect Disease Mechanisms Across Models.Annual review of genomics and human genetics · 2025
    Review
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  13. A platform for multimodalbioRxiv : the preprint server for biology · 2025
    Article
  14. Review
  15. Review
  16. Review
  17. Review
  18. Spatially ResolvedbioRxiv : the preprint server for biology · 2024
    Article
  19. Review
  20. The lncRNAGenes & development · 2024
    Article

13 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

5 authors at 2 institutions in 1 country.

Chong WangHoward Hughes Medical Institute, Harvard University, Cambridge, MA 02138.
Tian LuHoward Hughes Medical Institute, Harvard University, Cambridge, MA 02138.
George EmanuelHoward Hughes Medical Institute, Harvard University, Cambridge, MA 02138.
Hazen P BabcockCenter for Advanced Imaging, Harvard University, Cambridge, MA 02138.ORCID 0000-0003-4835-3692
Xiaowei ZhuangHoward Hughes Medical Institute, Harvard University, Cambridge, MA 02138; zhuang@chemistry.harvard.edu.ORCID 0000-0002-6034-7853
Howard Hughes Medical Institute · USHarvard University · US

Funding

Generation of novel cell type specific mouse genetic toolsU19MH114830 · NIMH · ALLEN INSTITUTE · PI NGAI, JOHN J. · 2017 to 2021
$64.7M
In situ transcriptome imaging in single cellsR01MH113094 · NIMH · HARVARD UNIVERSITY · PI DULAC, CATHERINE, ZHUANG, XIAOWEI · 2016 to 2020
$5.1M
Illuminating molecular mechanisms of cellular functions by single-molecule and super-resolution imagingR35GM122487 · NIGMS · HARVARD UNIVERSITY · PI ZHUANG, XIAOWEI · 2017 to 2021
$2.1M
Howard Hughes Medical InstituteNIGMS NIH HHS R35 GM122487NIMH NIH HHS R01 MH113094NIMH NIH HHS U19 MH114830
6 · The paper itself

Abstract

Pooled-library CRISPR screening provides a powerful means to discover genetic factors involved in cellular processes in a high-throughput manner. However, the phenotypes accessible to pooled-library screening are limited. Complex phenotypes, such as cellular morphology and subcellular molecular organization, as well as their dynamics, require imaging-based readout and are currently beyond the reach of pooled-library CRISPR screening. Here we report an all imaging-based pooled-library CRISPR screening approach that combines high-content phenotype imaging with high-throughput single guide RNA (sgRNA) identification in individual cells. In this approach, sgRNAs are codelivered to cells with corresponding barcodes placed at the 3' untranslated region of a reporter gene using a lentiviral delivery system with reduced recombination-induced sgRNA-barcode mispairing. Multiplexed error-robust fluorescence in situ hybridization (MERFISH) is used to read out the barcodes and hence identify the sgRNAs with high accuracy. We used this approach to screen 162 sgRNAs targeting 54 RNA-binding proteins for their effects on RNA localization to nuclear compartments and uncovered previously unknown regulatory factors for nuclear RNA localization. Notably, our screen revealed both positive and negative regulators for the nuclear speckle localization of a long noncoding RNA, MALAT1, suggesting a dynamic regulation of lncRNA localization in subcellular compartments.

Indexed as

RNA, Long NoncodingCell Line, TumorCell NucleusCRISPR-Cas SystemsGene EditingHigh-Throughput Nucleotide SequencingHumansImage Processing, Computer-AssistedIn Situ Hybridization, FluorescenceMolecular ProbesRNA-Binding ProteinsRNA, Guide, CRISPR-Cas SystemsSingle-Cell AnalysisMolecular ProbesRNA-Binding ProteinsRNA, Guide, CRISPR-Cas SystemsRNA, Long NoncodingCRISPRhigh-throughput screeningMERFISHnuclear compartmentsRNA localization

Identifiers

PMID31085639
PMCPMC6561216
OpenAlexW2945294402

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.