Evidence map›Paper›PMID 21151960›Full record

ArticlePLoS genetics2010

Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk.

Christin E Burd, William R Jeck, Yan Liu, Hanna K Sanoff, Zefeng Wang, Norman E Sharpless

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 513 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
513citing papers in PubMed, 2 pooled it
8.6field-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

513 citing papers in PubMed, 2 syntheses or guidelines pooled it, 918 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  4. Review
  5. Article
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  11. Role of Exosomal Non-Coding RNAsMicroRNA (Shariqah, United Arab Emirates) · 2026
    Review
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453 more citing papers are in PubMed but not listed here.

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 2 institutions in 1 country.

Christin E BurdThe Curriculum in Toxicology, The Lineberger Comprehensive Cancer Center, The University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
William R Jeck
Yan Liu
Hanna K Sanoff
Zefeng Wang
Norman E Sharpless
University of North Carolina at Chapel Hill · USUniversity of Virginia · US

Funding

UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Melissa A. Troester · 2001 to 2026
$36.3M
Integrated Training in Cancer Model SystemsT32CA009156 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J. · 1985 to 2020
$19.7M
TOXICOLOGYT32ES007126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ILONA JASPERS, Bernard E. Weissman · 1985 to 2026
$13.0M
The Role of p16INK4 in Mammalian AgingR01AG024379 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HE, SHENGHUI · 2004 to 2019
$4.6M
A Novel p16INK4a Reporter System to Assess Aging In VivoK99AG036817 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BURD, CHRISTIN E · 2010 to 2011
$147k
NCI NIH HHS CA009156-34NCI NIH HHS T32 CA009156NIA NIH HHS AG024379NIA NIH HHS K99 AG036817NIA NIH HHS K99AG036817NIA NIH HHS R01 AG024379NIEHS NIH HHS P30 ES010126NIEHS NIH HHS T32 ES007126
6 · The paper itself

Abstract

Human genome-wide association studies have linked single nucleotide polymorphisms (SNPs) on chromosome 9p21.3 near the INK4/ARF (CDKN2a/b) locus with susceptibility to atherosclerotic vascular disease (ASVD). Although this locus encodes three well-characterized tumor suppressors, p16(INK4a), p15(INK4b), and ARF, the SNPs most strongly associated with ASVD are ∼120 kb from the nearest coding gene within a long non-coding RNA (ncRNA) known as ANRIL (CDKN2BAS). While individuals homozygous for the atherosclerotic risk allele show decreased expression of ANRIL and the coding INK4/ARF transcripts, the mechanism by which such distant genetic variants influence INK4/ARF expression is unknown. Here, using rapid amplification of cDNA ends (RACE) and analysis of next-generation RNA sequencing datasets, we determined the structure and abundance of multiple ANRIL species. Each of these species was present at very low copy numbers in primary and cultured cells; however, only the expression of ANRIL isoforms containing exons proximal to the INK4/ARF locus correlated with the ASVD risk alleles. Surprisingly, RACE also identified transcripts containing non-colinear ANRIL exonic sequences, whose expression also correlated with genotype and INK4/ARF expression. These non-polyadenylated RNAs resisted RNAse R digestion and could be PCR amplified using outward-facing primers, suggesting they represent circular RNA structures that could arise from by-products of mRNA splicing. Next-generation DNA sequencing and splice prediction algorithms identified polymorphisms within the ASVD risk interval that may regulate ANRIL splicing and circular ANRIL (cANRIL) production. These results identify novel circular RNA products emanating from the ANRIL locus and suggest causal variants at 9p21.3 regulate INK4/ARF expression and ASVD risk by modulating ANRIL expression and/or structure.

Indexed as

AtherosclerosisCell Line, TumorCyclin-Dependent Kinase Inhibitor p15Cyclin-Dependent Kinase Inhibitor p16DNA, CircularExonsGene ExpressionGenome-Wide Association StudyHumansNucleic Acid ConformationRisk FactorsRNA SplicingRNA, UntranslatedCyclin-Dependent Kinase Inhibitor p15Cyclin-Dependent Kinase Inhibitor p16DNA, CircularRNA, Untranslated

Identifiers

PMID21151960
PMCPMC2996334
OpenAlexW1975909559

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.