Evidence map›Paper›PMID 25951186›Full record

ArticlePLoS genetics2015

The Zinc-Finger Antiviral Protein ZAP Inhibits LINE and Alu Retrotransposition.

John B Moldovan, John V Moran

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
108citing papers in PubMed, 1 pooled it
28.4field-weighted citation impact, top 1% 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

108 citing papers in PubMed, 1 synthesis or guideline pooled it, 143 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. LINE-1 Retrotransposons and Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2026
    Review
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48 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 1 country.

John B MoldovanCellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, Michigan, United States of America.
John V MoranCellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, Michigan, United States of America; Departments of Human Genetics and Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan, United States of America.
Michigan United · USUniversity of Michigan–Ann Arbor · US

Funding

CELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8M
Gen. &Mol. Analysis of Human LINE-1 RetrotranspositionR01GM060518 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORAN, JOHN V. · 1999 to 2024
$4.8M
Howard Hughes Medical InstituteNIGMS NIH HHS GM060518NIGMS NIH HHS R01 GM060518NIGMS NIH HHS T32 GM007315NIGMS NIH HHS T32GM007315
6 · The paper itself

Abstract

Long INterspersed Element-1 (LINE-1 or L1) is the only active autonomous retrotransposon in the human genome. To investigate the interplay between the L1 retrotransposition machinery and the host cell, we used co-immunoprecipitation in conjunction with liquid chromatography and tandem mass spectrometry to identify cellular proteins that interact with the L1 first open reading frame-encoded protein, ORF1p. We identified 39 ORF1p-interacting candidate proteins including the zinc-finger antiviral protein (ZAP or ZC3HAV1). Here we show that the interaction between ZAP and ORF1p requires RNA and that ZAP overexpression in HeLa cells inhibits the retrotransposition of engineered human L1 and Alu elements, an engineered mouse L1, and an engineered zebrafish LINE-2 element. Consistently, siRNA-mediated depletion of endogenous ZAP in HeLa cells led to a ~2-fold increase in human L1 retrotransposition. Fluorescence microscopy in cultured human cells demonstrated that ZAP co-localizes with L1 RNA, ORF1p, and stress granule associated proteins in cytoplasmic foci. Finally, molecular genetic and biochemical analyses indicate that ZAP reduces the accumulation of full-length L1 RNA and the L1-encoded proteins, yielding mechanistic insight about how ZAP may inhibit L1 retrotransposition. Together, these data suggest that ZAP inhibits the retrotransposition of LINE and Alu elements.

Indexed as

Alu ElementsRetroelementsAnimalsChromatography, LiquidHeLa CellsHumansImmunoprecipitationLong Interspersed Nucleotide ElementsMiceOpen Reading FramesPlasmidsRNA-Binding ProteinsTandem Mass SpectrometryZebrafishRetroelementsRNA-Binding ProteinsZC3HAV1 protein, human

Identifiers

PMID25951186
PMCPMC4423928
OpenAlexW364316428

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.