Evidence map›Paper›PMID 38937837›Full record

ArticleMobile DNA2024

Subcellular location of L1 retrotransposon-encoded ORF1p, reverse transcription products, and DNA sensors in lupus granulocytes.

Fatemeh Moadab, Sepideh Sohrabi, Xiaoxing Wang, Rayan Najjar, Justina C Wolters, Hua Jiang, Wenyan Miao, Donna Romero, Dennis M Zaller, Megan Tran and 5 more

Abstract read
In one paragraph

Article in Mobile DNA, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
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

15 authors.

Fatemeh MoadabDivision of Rheumatology, Department of Medicine, University of Washington, Seattle, WA, USA.
Sepideh SohrabiDivision of Rheumatology, Department of Medicine, University of Washington, Seattle, WA, USA.
Xiaoxing WangDivision of Rheumatology, Department of Medicine, University of Washington, Seattle, WA, USA.
Rayan NajjarDivision of Rheumatology, Department of Medicine, University of Washington, Seattle, WA, USA.
Justina C WoltersDepartment of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Hua JiangLaboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY, USA.
Wenyan MiaoROME Therapeutics, Boston, MA, USA.
Donna RomeroROME Therapeutics, Boston, MA, USA.
Dennis M ZallerROME Therapeutics, Boston, MA, USA.
Megan TranDivision of Rheumatology, Department of Medicine, University of Washington, Seattle, WA, USA.
Alison BaysDivision of Rheumatology, Department of Medicine, University of Washington, Seattle, WA, USA.
Martin S TaylorDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Rosana KapellerROME Therapeutics, Boston, MA, USA.
John LaCavaLaboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY, USA.
Tomas MustelinDivision of Rheumatology, Department of Medicine, University of Washington, Seattle, WA, USA. tomas2@uw.edu.

Funding

RESEARCH TRAINING IN RHEUMATOLOGYT32AR007108 · NIAMS · UNIVERSITY OF WASHINGTON · PI Shaun Jackson, Tomas M Mustelin · 1986 to 2026
$6.6M
Upstream drivers of type I interferons in lupusR01AI186337 · NIAID · UNIVERSITY OF WASHINGTON · PI Joanne Michelle Kahlenberg, John LaCava · 2024 to 2026
$2.3M
Role of the L1 retrotransposon in interferon-positive SLER01AR081654 · NIAMS · UNIVERSITY OF WASHINGTON · PI Tomas M Mustelin · 2023 to 2026
$2.1M
Role of protein citrullination in rheumatoid arthritisR01AR074939 · NIAMS · UNIVERSITY OF WASHINGTON · PI MUSTELIN, TOMAS M · 2020 to 2024
$1.9M
Elucidating structural, mechanistic, and allosteric determinants of mTOR Complex 2 (mTORC2) signaling.K08DK129824 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI TAYLOR, MARTIN S · 2021 to 2025
$853k
Alternative splicing and expression of transposable elements in aging skeletal muscleR21AG087517 · NIA · UNIVERSITY OF WASHINGTON · PI MUSTELIN, TOMAS M · 2024 to 2024
$485k
The roots of SLE: Can we cure it with a reverse transcriptase inhibitor?R21AR075134 · NIAMS · UNIVERSITY OF WASHINGTON · PI MUSTELIN, TOMAS M · 2019 to 2020
$427k
CSR NIH HHS R21 AR075134, R01 AR074939, and R01 AR081654NIAID NIH HHS R01 AI186337NIAMS NIH HHS R01 AR074939NIAMS NIH HHS R01 AR081654NIAMS NIH HHS R21 AR075134NIAMS NIH HHS T32 AR007108NIA NIH HHS R21 AG087517NIDDK NIH HHS K08 DK129824Rockefeller University Cooperative Centers on Human Immunology (NIAID) Infrastructure and Opportunity Fund N/A
6 · The paper itself

Abstract

backgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with an unpredictable course of recurrent exacerbations alternating with more stable disease. SLE is characterized by broad immune activation and autoantibodies against double-stranded DNA and numerous proteins that exist in cells as aggregates with nucleic acids, such as Ro60, MOV10, and the L1 retrotransposon-encoded ORF1p.

resultsHere we report that these 3 proteins are co-expressed and co-localized in a subset of SLE granulocytes and are concentrated in cytosolic dots that also contain DNA: RNA heteroduplexes and the DNA sensor ZBP1, but not cGAS. The DNA: RNA heteroduplexes vanished from the neutrophils when they were treated with a selective inhibitor of the L1 reverse transcriptase. We also report that ORF1p granules escape neutrophils during the extrusion of neutrophil extracellular traps (NETs) and, to a lesser degree, from neutrophils dying by pyroptosis, but not apoptosis.

conclusionsThese results bring new insights into the composition of ORF1p granules in SLE neutrophils and may explain, in part, why proteins in these granules become targeted by autoantibodies in this disease.

Indexed as

AutoantibodiesCGASL1MOV10NeutrophilsRetrotransposonSystemic lupus erythematosusZBP1Z-DNA

Identifiers

PMID38937837
PMCPMC11212426

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.