ReviewGenes, brain, and behavior2021
A long non-coding RNA (Lrap) modulates brain gene expression and levels of alcohol consumption in rats.
Review in Genes, brain, and behavior, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- The importance of non-coding RNAs in environmental stress-related developmental brain disorders: A systematic review of evidence associated with exposure to alcohol, anesthetic drugs, nicotine, and viral infections.Neuroscience and biobehavioral reviews · 2021Pooled it
- Genetic modulation of protein expression in rat brain.iScience · 2025Article
- Noncoding RNA and Alcohol Use Disorder: A Scoping Review of Current Research and Knowledge Gaps.Alcohol research : current reviews · 2025Article
- It is not just about transcription: involvement of brain RNA splicing in substance use disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- The genetical genomic path to understanding why rats and humans consume too much alcohol.Journal of neurobiology and physiology · 2024Article
- How life events may confer vulnerability to addiction: the role of epigenetics.Frontiers in molecular neuroscience · 2024Review
- Post-translational modifications of histone and non-histone proteins in epigenetic regulation and translational applications in alcohol-associated liver disease: Challenges and research opportunities.Pharmacology & therapeutics · 2023Review
- Functional roles, regulatory mechanisms and theranostics applications of ncRNAs in alcohol use disorder.International journal of biological sciences · 2023Review
- RCFGL: Rapid Condition adaptive Fused Graphical Lasso and application to modeling brain region co-expression networks.PLoS computational biology · 2023Article
- Effect of chronic intermittent ethanol vapor exposure on RNA content of brain-derived extracellular vesicles.Alcohol (Fayetteville, N.Y.) · 2022Article
- Developmental origins of adult diseases.Medical review (2021) · 2022Review
- Of mice and human-specific long noncoding RNAs.Mammalian genome : official journal of the International Mammalian Genome Society · 2022Review
- Non-coding RNA in alcohol use disorder by affecting synaptic plasticity.Experimental brain research · 2022Review
- Beyond Genes: Inclusion of Alternative Splicing and Alternative Polyadenylation to Assess the Genetic Architecture of Predisposition to Voluntary Alcohol Consumption in Brain of the HXB/BXH Recombinant Inbred Rat Panel.Frontiers in genetics · 2022Article
- Hippocampal ceRNA networks from chronic intermittent ethanol vapor-exposed male mice and functional analysis of top-ranked lncRNA genes for ethanol drinking phenotypes.Advances in drug and alcohol research · 2022Article
- A long non-coding RNA (Lrap) modulates brain gene expression and levels of alcohol consumption in rats.Genes, brain, and behavior · 2021Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
LncRNAs are important regulators of quantitative and qualitative features of the transcriptome. We have used QTL and other statistical analyses to identify a gene coexpression module associated with alcohol consumption. The "hub gene" of this module, Lrap (Long non-coding RNA for alcohol preference), was an unannotated transcript resembling a lncRNA. We used partial correlation analyses to establish that Lrap is a major contributor to the integrity of the coexpression module. Using CRISPR/Cas9 technology, we disrupted an exon of Lrap in Wistar rats. Measures of alcohol consumption in wild type, heterozygous and knockout rats showed that disruption of Lrap produced increases in alcohol consumption/alcohol preference. The disruption of Lrap also produced changes in expression of over 700 other transcripts. Furthermore, it became apparent that Lrap may have a function in alternative splicing of the affected transcripts. The GO category of "Response to Ethanol" emerged as one of the top candidates in an enrichment analysis of the differentially expressed transcripts. We validate the role of Lrap as a mediator of alcohol consumption by rats, and also implicate Lrap as a modifier of the expression and splicing of a large number of brain transcripts. A defined subset of these transcripts significantly impacts alcohol consumption by rats (and possibly humans). Our work shows the pleiotropic nature of non-coding elements of the genome, the power of network analysis in identifying the critical elements influencing phenotypes, and the fact that not all changes produced by genetic editing are critical for the concomitant changes in phenotype.
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Registered trials
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.