Evidence map›Paper›PMID 35410423›Full record

ArticleNature communications2022

Reprogrammed tracrRNAs enable repurposing of RNAs as crRNAs and sequence-specific RNA biosensors.

Yang Liu, Filipe Pinto, Xinyi Wan, Zhugen Yang, Shuguang Peng, Mengxi Li, Jonathan M Cooper, Zhen Xie, Christopher E French, Baojun Wang

Abstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
–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

25 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Engineering CRISPR guide RNAs for programmable RNA sensors.Biochemical Society transactions · 2023
    Pooled it
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  4. Programming Next-Generation Synthetic Biosensors by Genetic Circuit Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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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

10 authors.

Yang LiuCollege of Chemical and Biological Engineering & Hangzhou Innovation Center, Zhejiang University, Hangzhou, 311200, China.
Filipe Pinto *Centre for Synthetic and Systems Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FF, UK.ORCID 0000-0002-8554-6648
Xinyi Wan *Centre for Synthetic and Systems Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FF, UK.ORCID 0000-0002-5250-9277
Zhugen YangResearch Centre for Biological Computation, Zhejiang Laboratory, Hangzhou, 311100, China.ORCID 0000-0003-4183-8160
Shuguang PengCenter for Synthetic and System Biology, Department of Automation, Beijing National Research Centre for Information Science and Technology, Tsinghua University, Beijing, 100084, China.
Mengxi LiCentre for Synthetic and Systems Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FF, UK.
Jonathan M CooperDivision of Biomedical Engineering, James Watt School of Engineering, University of Glasgow, Glasgow, G12 8QQ, UK.ORCID 0000-0002-2358-1050
Zhen XieCenter for Synthetic and System Biology, Department of Automation, Beijing National Research Centre for Information Science and Technology, Tsinghua University, Beijing, 100084, China.ORCID 0000-0001-8798-9592
Christopher E FrenchCentre for Synthetic and Systems Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FF, UK.
Baojun WangCollege of Chemical and Biological Engineering & Hangzhou Innovation Center, Zhejiang University, Hangzhou, 311200, China. baojun.wang@zju.edu.cn.ORCID 0000-0002-4858-8937

Funding

Department of HealthMedical Research Council MR/S018875/1Medical Research Council MR/V035401/1Wellcome Trust
6 · The paper itself

Abstract

In type II CRISPR systems, the guide RNA (gRNA) comprises a CRISPR RNA (crRNA) and a hybridized trans-acting CRISPR RNA (tracrRNA), both being essential in guided DNA targeting functions. Although tracrRNAs are diverse in sequence and structure across type II CRISPR systems, the programmability of crRNA-tracrRNA hybridization for Cas9 is not fully understood. Here, we reveal the programmability of crRNA-tracrRNA hybridization for Streptococcus pyogenes Cas9, and in doing so, redefine the capabilities of Cas9 proteins and the sources of crRNAs, providing new biosensing applications for type II CRISPR systems. By reprogramming the crRNA-tracrRNA hybridized sequence, we show that engineered crRNA-tracrRNA interactions can not only enable the design of orthogonal cellular computing devices but also facilitate the hijacking of endogenous small RNAs/mRNAs as crRNAs. We subsequently describe how these re-engineered gRNA pairings can be implemented as RNA sensors, capable of monitoring the transcriptional activity of various environment-responsive genomic genes, or detecting SARS-CoV-2 RNA in vitro, as an Atypical gRNA-activated Transcription Halting Alarm (AGATHA) biosensor.

Indexed as

Biosensing TechniquesCOVID-19CRISPR-Cas SystemsHumansRNA, Guide, CRISPR-Cas SystemsRNA, ViralSARS-CoV-2RNA, Guide, CRISPR-Cas SystemsRNA, Viral

Identifiers

PMID35410423
PMCPMC9001733

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.