Evidence map›Paper›PMID 22912586›Full record

ArticlePLoS genetics2012

Rescuing Alu: recovery of new inserts shows LINE-1 preserves Alu activity through A-tail expansion.

Bradley J Wagstaff, Dale J Hedges, Rebecca S Derbes, Rebeca Campos Sanchez, Francesca Chiaromonte, Kateryna D Makova, Astrid M Roy-Engel

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
6.0field-weighted citation impact, top 4% 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

31 citing papers in PubMed, 44 citations in OpenAlex.

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  16. Coevolution between transposable elements and recombination.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017
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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

7 authors at 3 institutions in 1 country.

Bradley J WagstaffTulane Cancer Center, Department of Epidemiology, Tulane University, New Orleans, Louisiana, United States of America.
Dale J Hedges
Rebecca S Derbes
Rebeca Campos Sanchez
Francesca Chiaromonte
Kateryna D Makova
Astrid M Roy-Engel
Pennsylvania State University · USTulane University · USUniversity of Miami · US

Funding

UNCOVERING THE MECHANISMS OF OSTEOSARCOMA METASTASIS SUPPRESSION BY MTBPP20RR020152 · NCRR · TULANE UNIVERSITY OF LOUISIANA · PI DEININGER, PRESCOTT L. · 2004 to 2011
$17.0M
Mentoring a Cancer Genetics ProgramP20GM103518 · NIGMS · TULANE UNIVERSITY OF LOUISIANA · PI DEININGER, PRESCOTT L. · 2012 to 2013
$4.3M
Regulatory effects of LINE components on SINE mobilizationR01GM079709 · NIGMS · TULANE UNIVERSITY OF LOUISIANA · PI ENGEL, ASTRID M · 2008 to 2012
$1.4M
Male Mutation Bias and Paternal Age Effect in MammalsR01GM072264 · NIGMS · PENNSYLVANIA STATE UNIVERSITY-UNIV PARK · PI MAKOVA, KATERYNA · 2004 to 2010
$1.2M
NCRR NIH HHS P20 RR020152NCRR NIH HHS P20RR020152NIGMS NIH HHS P20 GM103518NIGMS NIH HHS R01 GM072264NIGMS NIH HHS R01GM072264NIGMS NIH HHS R01 GM079709NIGMS NIH HHS R01GM079709A
6 · The paper itself

Abstract

Alu elements are trans-mobilized by the autonomous non-LTR retroelement, LINE-1 (L1). Alu-induced insertion mutagenesis contributes to about 0.1% human genetic disease and is responsible for the majority of the documented instances of human retroelement insertion-induced disease. Here we introduce a SINE recovery method that provides a complementary approach for comprehensive analysis of the impact and biological mechanisms of Alu retrotransposition. Using this approach, we recovered 226 de novo tagged Alu inserts in HeLa cells. Our analysis reveals that in human cells marked Alu inserts driven by either exogenously supplied full length L1 or ORF2 protein are indistinguishable. Four percent of de novo Alu inserts were associated with genomic deletions and rearrangements and lacked the hallmarks of retrotransposition. In contrast to L1 inserts, 5' truncations of Alu inserts are rare, as most of the recovered inserts (96.5%) are full length. De novo Alus show a random pattern of insertion across chromosomes, but further characterization revealed an Alu insertion bias exists favoring insertion near other SINEs, highly conserved elements, with almost 60% landing within genes. De novo Alu inserts show no evidence of RNA editing. Priming for reverse transcription rarely occurred within the first 20 bp (most 5') of the A-tail. The A-tails of recovered inserts show significant expansion, with many at least doubling in length. Sequence manipulation of the construct led to the demonstration that the A-tail expansion likely occurs during insertion due to slippage by the L1 ORF2 protein. We postulate that the A-tail expansion directly impacts Alu evolution by reintroducing new active source elements to counteract the natural loss of active Alus and minimizing Alu extinction.

Indexed as

Mutagenesis, Insertional3' Flanking Region5' Flanking RegionAlu ElementsBase SequenceEndonucleasesEvolution, MolecularExonsGenome, HumanHeLa CellsHumansIntronsLong Interspersed Nucleotide ElementsMolecular Sequence DataReverse TranscriptionRNA-Directed DNA PolymeraseEndonucleasesORF2 protein, humanRNA-Directed DNA Polymerase

Identifiers

PMID22912586
PMCPMC3415434
OpenAlexW2082996197

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.