Evidence map›Paper›PMID 40226913›Full record

ArticleNucleic acids research2025

CRISPR RNA binding drives structural ordering that primes Cas7-11 for target cleavage.

Calvin P Lin, Harry Li, Daniel J Brogan, Tianqi Wang, Omar S Akbari, Elizabeth A Komives

Abstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Calvin P LinDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, United States.
Harry LiDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, United States.
Daniel J BroganSchool of Biological Sciences, Department of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA92093, United States.
Tianqi WangSchool of Biological Sciences, Department of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA92093, United States.
Omar S AkbariSchool of Biological Sciences, Department of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA92093, United States.ORCID 0000-0002-6853-9884
Elizabeth A KomivesDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, United States.ORCID 0000-0001-5264-3866

Funding

MOLECULAR BIOPHYSICS TRAINING PROGRAMT32GM008326 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOMIVES, ELIZABETH A. · 1989 to 2020
$7.5M
Precision guided SIT for the control of vector-borne diseaseR01AI151004 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AKBARI, OMAR SULTAN · 2020 to 2024
$2.3M
NIAID NIH HHS R01 AI151004NIAID NIH HHS R01AI151004NIGMS NIH HHS T32 GM008326NIH HHS T32 GM008326
6 · The paper itself

Abstract

Type III-E CRISPR-Cas effectors, referred to as Cas7-11 or giant Repeat-Associated Mysterious Protein, are single proteins that cleave target RNAs (tgRNAs) without nonspecific collateral cleavage, opening new possibilities for RNA editing. Here, biochemical assays combined with amide hydrogen-deuterium exchange mass spectrometry (HDX-MS) experiments reveal the dynamics of apo Cas7-11. The HDX-MS results suggest a mechanism by which CRISPR RNA (crRNA) stabilizes the folded state of the protein and subsequent tgRNA binding remodels it to the active form. HDX-MS shows that the four Cas7 RNA recognition motif (RRM) folds are well-folded, but insertion sequences, including disordered catalytic loops and β-hairpins of the Cas7.2/Cas7.3 active sites, fold upon binding crRNA leading to stronger interactions at domain-domain interfaces, and folding of the Cas7.1 processing site. TgRNA binding causes conformational changes around the catalytic loops of Cas7.2 and Cas7.3. We show that Cas7-11 cannot independently process the CRISPR array and that binding of partially processed crRNA induces multiple states in Cas7-11 and reduces tgRNA cleavage. The insertion domain interacts most stably with mature crRNA. Finally, we show a crRNA-induced conformational change in one of the tetratricopeptide repeat fused with Cas/HEF1-associated signal transducer (TPR-CHAT) binding sites providing an explanation for why crRNA binding facilitates TPR-CHAT binding.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated ProteinsCRISPR-Cas SystemsRNACatalytic DomainHydrogen Deuterium Exchange-Mass SpectrometryModels, MolecularProtein BindingRNA Recognition MotifCRISPR-Associated ProteinsRNA

Identifiers

PMID40226913
PMCPMC11995262

What OpenQuestion holds

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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.