Evidence map›Paper›PMID 37398409›Full record

ArticlebioRxiv : the preprint server for biology2023

Programmable RNA-guided endonucleases are widespread in eukaryotes and their viruses.

Kaiyi Jiang, Justin Lim, Samantha Sgrizzi, Michael Trinh, Alisan Kayabolen, Natalya Yutin, Eugene V Koonin, Omar O Abudayyeh, Jonathan S Gootenberg

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 6 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Kaiyi JiangMcGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Justin LimMcGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Samantha SgrizziMcGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Michael TrinhMcGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Alisan KayabolenMcGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Natalya YutinNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Eugene V KooninNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Omar O AbudayyehMcGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jonathan S GootenbergMcGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
McGovern Institute for Brain Research · USNational Institutes of Health · US

Funding

Discovery and manipulation of transcription factors to restore long term stem cell repopulation in aged bone-marrowR01AG074932 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Omar O Abudayyeh, Jonathan Samuel Gootenberg · 2022 to 2026
$3.3M
Programmable gene integration and cell engineering with CRISPR-directed integrasesR01EB031957 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ABUDAYYEH, OMAR O, GOOTENBERG, JONATHAN SAMUEL · 2021 to 2024
$2.4M
Systematic discovery, characterization, and design of novel genome editing and delivery tools using a high-throughput metagenomic screening pipelineR21AI149694 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ABUDAYYEH, OMAR O, GOOTENBERG, JONATHAN SAMUEL · 2020 to 2021
$414k
RNA targeting tools with novel specific RNA-guided RNA-targeting CRISPR effectorsR56HG011857 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ABUDAYYEH, OMAR O, GOOTENBERG, JONATHAN SAMUEL · 2021 to 2021
$363k
NHGRI NIH HHS R56 HG011857NIAID NIH HHS R21 AI149694NIA NIH HHS R01 AG074932NIBIB NIH HHS R01 EB031957
6 · The paper itself

Abstract

TnpB proteins are RNA-guided nucleases that are broadly associated with IS200/605 family transposons in prokaryotes. TnpB homologs, named Fanzors, have been detected in genomes of some eukaryotes and large viruses, but their activity and functions in eukaryotes remain unknown. We searched genomes of diverse eukaryotes and their viruses for TnpB homologs and identified numerous putative RNA-guided nucleases that are often associated with various transposases, suggesting they are encoded in mobile genetic elements. Reconstruction of the evolution of these nucleases, which we rename Horizontally-transferred Eukaryotic RNA-guided Mobile Element Systems (HERMES), revealed multiple acquisitions of TnpBs by eukaryotes and subsequent diversification. In their adaptation and spread in eukaryotes, HERMES proteins acquired nuclear localization signals, and genes captured introns, indicating extensive, long term adaptation to functioning in eukaryotic cells. Biochemical and cellular evidence show that HERMES employ non-coding RNAs encoded adjacent to the nuclease for RNA-guided cleavage of double-stranded DNA. HERMES nucleases contain a re-arranged catalytic site of the RuvC domain, similar to a distinct subset of TnpBs, and lack collateral cleavage activity. We demonstrate that HERMES can be harnessed for genome editing in human cells, highlighting the potential of these widespread eukaryotic RNA-guided nucleases for biotechnology applications.

Identifiers

PMID37398409
PMCPMC10312701
OpenAlexW4380550569

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.