Evidence map›Paper›PMID 24101588›Full record

ArticleNucleic acids research2014

Human LINE-1 restriction by APOBEC3C is deaminase independent and mediated by an ORF1p interaction that affects LINE reverse transcriptase activity.

Axel V Horn, Sabine Klawitter, Ulrike Held, André Berger, Ananda Ayyappan Jaguva Vasudevan, Anja Bock, Henning Hofmann, Kay-Martin O Hanschmann, Jan-Hendrik Trösemeier, Egbert Flory and 6 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
12.0field-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

51 citing papers in PubMed, 85 citations in OpenAlex.

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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

16 authors at 1 institution in 1 country.

Axel V HornSection PR2/Retroelements, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany, Department of Embryology, Carnegie Institution of Washington, 3520 San Martin Drive, Baltimore, MD 21218, USA, Division of Medical Biotechnology, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany, Clinic for Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany and Biostatistics Section, Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany.
Sabine Klawitter
Ulrike Held
André Berger
Ananda Ayyappan Jaguva Vasudevan
Anja Bock
Henning Hofmann
Kay-Martin O Hanschmann
Jan-Hendrik Trösemeier
Egbert Flory
Robert A Jabulowsky
Jeffrey S Han
Johannes Löwer
Roswitha Löwer
Carsten Münk
Gerald G Schumann
Carnegie Institution for Science · US

Funding

Using budding yeast to study LINE (L1) retrotranspositionR01GM090192 · NIGMS · TULANE UNIVERSITY OF LOUISIANA · PI HAN, JEFFREY S · 2010 to 2014
$1.4M
NIGMS NIH HHS R01 GM090192
6 · The paper itself

Abstract

LINE-1 (L1) retrotransposons are mobile genetic elements whose extensive proliferation resulted in the generation of ≈ 34% of the human genome. They have been shown to be a cause of single-gene diseases. Moreover, L1-encoded endonuclease can elicit double-strand breaks that may lead to genomic instability. Mammalian cells adopted strategies restricting mobility and deleterious consequences of uncontrolled retrotransposition. The human APOBEC3 protein family of polynucleotide cytidine deaminases contributes to intracellular defense against retroelements. APOBEC3 members inhibit L1 retrotransposition by 35-99%. However, genomic L1 retrotransposition events that occurred in the presence of L1-restricting APOBEC3 proteins are devoid of detectable G-to-A hypermutations, suggesting one or multiple deaminase-independent L1 restricting mechanisms. We set out to uncover the mechanism of APOBEC3C (A3C)-mediated L1 inhibition and found that it is deaminase independent, requires an intact dimerization site and the RNA-binding pocket mutation R122A abolishes L1 restriction by A3C. Density gradient centrifugation of L1 ribonucleoprotein particles, subcellular co-localization of L1-ORF1p and A3C and co-immunoprecipitation experiments indicate that an RNA-dependent physical interaction between L1 ORF1p and A3C dimers is essential for L1 restriction. Furthermore, we demonstrate that the amount of L1 complementary DNA synthesized by L1 reverse transcriptase is reduced by ≈ 50% if overexpressed A3C is present.

Indexed as

Long Interspersed Nucleotide ElementsCarrier ProteinsCytidine DeaminaseCytoplasmic GranulesDNA HelicasesHeLa CellsHumansMutationPoly-ADP-Ribose Binding ProteinsProtein MultimerizationProteinsRNA-Directed DNA PolymeraseRNA HelicasesRNA Recognition Motif ProteinsAPOBEC3A protein, humanAPOBEC3C protein, humanCarrier ProteinsCytidine DeaminaseDNA HelicasesG3BP1 protein, humanORF1 protein, humanPoly-ADP-Ribose Binding ProteinsProteinsRNA-Directed DNA PolymeraseRNA HelicasesRNA Recognition Motif Proteins

Identifiers

PMID24101588
PMCPMC3874205
OpenAlexW2010268348

What OpenQuestion holds

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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.