Evidence map›Paper›PMID 29059299›Full record

ArticleNucleic acids research2017

A cautionary tale of sense-antisense gene pairs: independent regulation despite inverse correlation of expression.

Ashish Goyal, Evgenij Fiškin, Tony Gutschner, Maria Polycarpou-Schwarz, Matthias Groß, Julia Neugebauer, Minakshi Gandhi, Maiwen Caudron-Herger, Vladimir Benes, Sven Diederichs

Abstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
–field-weighted citation impact
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

30 citing papers in PubMed.

  1. Article
  2. Review
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  5. Review
  6. Review
  7. Article
  8. lncHUB2: aggregated and inferred knowledge about human and mouse lncRNAs.Database : the journal of biological databases and curation · 2023
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
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  15. Article
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  19. Article
  20. An MXD1-derived repressor peptide identifies noncoding mediators of MYC-driven cell proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
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

10 authors.

Ashish GoyalDivision of RNA Biology & Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Evgenij FiškinDivision of RNA Biology & Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Tony GutschnerDivision of RNA Biology & Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Maria Polycarpou-SchwarzDivision of RNA Biology & Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Matthias GroßDivision of RNA Biology & Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Julia NeugebauerDivision of RNA Biology & Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Minakshi GandhiDivision of RNA Biology & Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Maiwen Caudron-HergerDivision of RNA Biology & Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Vladimir BenesGenomics Core Facility, EMBL Heidelberg, 69117 Heidelberg, Germany.
Sven DiederichsDivision of RNA Biology & Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Long non-coding RNAs (lncRNAs) have been proven to play important roles in diverse cellular processes including the DNA damage response. Nearly 40% of annotated lncRNAs are transcribed in antisense direction to other genes and have often been implicated in their regulation via transcript- or transcription-dependent mechanisms. However, it remains unclear whether inverse correlation of gene expression would generally point toward a regulatory interaction between the genes. Here, we profiled lncRNA and mRNA expression in lung and liver cancer cells after exposure to DNA damage. Our analysis revealed two pairs of mRNA-lncRNA sense-antisense transcripts being inversely expressed upon DNA damage. The lncRNA NOP14-AS1 was strongly upregulated upon DNA damage, while the mRNA for NOP14 was downregulated, both in a p53-dependent manner. For another pair, the lncRNA LIPE-AS1 was downregulated, while its antisense mRNA CEACAM1 was upregulated. To test whether as expected the antisense genes would regulate each other resulting in this highly significant inverse correlation, we employed antisense oligonucleotides and RNAi to study transcript-dependent effects as well as dCas9-based transcriptional modulation by CRISPRi/CRISPRa for transcription-dependent effects. Surprisingly, despite the strong stimulus-dependent inverse correlation, our data indicate that neither transcript- nor transcription-dependent mechanisms explain the inverse regulation of NOP14-AS1:NOP14 or LIPE-AS1:CEACAM1 expression. Hence, sense-antisense pairs whose expression is strongly-positively or negatively-correlated can be nonetheless regulated independently. This highlights the requirement of individual experimental studies for each antisense pair and prohibits drawing conclusions on regulatory mechanisms from expression correlations.

Indexed as

Gene Expression RegulationCell LineDNA DamageHumansNuclear ProteinsRNA, AntisenseRNA, MessengerTumor Suppressor Protein p53NOP14 protein, humanNuclear ProteinsRNA, AntisenseRNA, MessengerTumor Suppressor Protein p53

Identifiers

PMID29059299
PMCPMC5716207

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Registered trials

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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.