Evidence map›Paper›PMID 37114770›Full record

ArticleeLife2023

Condensation of LINE-1 is critical for retrotransposition.

Srinjoy Sil, Sarah Keegan, Farida Ettefa, Lance T Denes, Jef D Boeke, Liam J Holt

Open access · goldAbstract read
In one paragraph

Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
10.7field-weighted citation impact, top 2% 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

17 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. From the genome's perspective: Bearing somatic retrotransposition to leverage the regulatory potential of L1 RNAs.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. A prion-like domain in Gag capsid protein drives retrotransposon particle assembly and mobility.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  14. Article
  15. Article
  16. Article
  17. 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

6 authors at 1 institution in 1 country.

Srinjoy SilInstitute for Systems Genetics, New York University Langone Medical Center, New York, United States.ORCID 0000-0002-6722-4311
Sarah KeeganInstitute for Systems Genetics, New York University Langone Medical Center, New York, United States.
Farida EttefaInstitute for Systems Genetics, New York University Langone Medical Center, New York, United States.
Lance T DenesInstitute for Systems Genetics, New York University Langone Medical Center, New York, United States.
Jef D BoekeInstitute for Systems Genetics, New York University Langone Medical Center, New York, United States.ORCID 0000-0001-5322-4946
Liam J HoltInstitute for Systems Genetics, New York University Langone Medical Center, New York, United States.ORCID 0000-0002-4002-0861
NYU Langone Health · US

Funding

Somatic Activation of Retrotransposition: A New Molecular Mechanism of Aging?P01AG051449 · NIA · BROWN UNIVERSITY · PI Jef D BOEKE · 2016 to 2026
$30.4M
MEDICAL SCIENTIST TRAININGT32GM007308 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI PHILIPS, MARK REID · 1985 to 2019
$23.2M
The Physical Biology of Neurodegeneration in Sporadic Amyotrophic Lateral Sclerosis/Frontotemporal DementiaR01NS127186 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HOLT, LIAM J, PHATNANI, HEMALI · 2021 to 2025
$8.2M
Medical Scientist Research Service AwardT32GM136573 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SULMAN, ERIK · 2020 to 2024
$6.8M
Cancer under pressure: Mechanisms of adaptation to compressive stressR37CA240765 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI HOLT, LIAM J · 2019 to 2025
$3.2M
Tools to probe the biophysical properties of cellsR01GM132447 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI HOLT, LIAM J · 2019 to 2022
$2.1M
NCI NIH HHS R37 CA240765NIA NIH HHS P01 AG051449NIGMS NIH HHS R01 GM132447NIGMS NIH HHS T32 GM007308NIGMS NIH HHS T32 GM136573NINDS NIH HHS R01 NS127186
6 · The paper itself

Abstract

LINE-1 (L1) is the only autonomously active retrotransposon in the human genome, and accounts for 17% of the human genome. The L1 mRNA encodes two proteins, ORF1p and ORF2p, both essential for retrotransposition. ORF2p has reverse transcriptase and endonuclease activities, while ORF1p is a homotrimeric RNA-binding protein with poorly understood function. Here, we show that condensation of ORF1p is critical for L1 retrotransposition. Using a combination of biochemical reconstitution and live-cell imaging, we demonstrate that electrostatic interactions and trimer conformational dynamics together tune the properties of ORF1p assemblies to allow for efficient L1 ribonucleoprotein (RNP) complex formation in cells. Furthermore, we relate the dynamics of ORF1p assembly and RNP condensate material properties to the ability to complete the entire retrotransposon life-cycle. Mutations that prevented ORF1p condensation led to loss of retrotransposition activity, while orthogonal restoration of coiled-coil conformational flexibility rescued both condensation and retrotransposition. Based on these observations, we propose that dynamic ORF1p oligomerization on L1 RNA drives the formation of an L1 RNP condensate that is essential for retrotransposition.

Indexed as

Long Interspersed Nucleotide ElementsRetroelementsHumansMutationRNARNA-Binding ProteinsRetroelementsRNARNA-Binding Proteinsbiochemistrybiophysicscell biologychemical biologycondensatesevolutionhumanLINE-1phase separationretrotransposons

Identifiers

PMID37114770
PMCPMC10202459
OpenAlexW4367297977

What OpenQuestion 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 OpenQuestion graph.