Evidence map›Paper›PMID 27406820›Full record

ArticleEMBO molecular medicine2016

Oligonucleotide-induced alternative splicing of serotonin 2C receptor reduces food intake.

Zhaiyi Zhang, Manli Shen, Paul J Gresch, Masoud Ghamari-Langroudi, Alexander G Rabchevsky, Ronald B Emeson, Stefan Stamm

Open access · goldAbstract read
In one paragraph

Article in EMBO molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

21 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Emerging Functions for snoRNAs and snoRNA-Derived Fragments.International journal of molecular sciences · 2021
    Review
  8. Review
  9. Article
  10. Review
  11. Functional diversity of small nucleolar RNAs.Nucleic acids research · 2020
    Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Alternative mRNA Splicing in the Pathogenesis of Obesity.International journal of molecular sciences · 2018
    Review
  17. Review
  18. C/D-box snoRNAs form methylating and non-methylating ribonucleoprotein complexes: Old dogs show new tricks.BioEssays : news and reviews in molecular, cellular and developmental biology · 2017
    Review
  19. Serotonergic Control of Metabolic Homeostasis.Frontiers in cellular neuroscience · 2017
    Review
  20. 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

7 authors at 2 institutions in 1 country.

Zhaiyi ZhangDepartment of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA.
Manli ShenDepartment of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA.
Paul J GreschDepartment of Pharmacology, Vanderbilt University, Nashville, TN, USA.
Masoud Ghamari-LangroudiDepartment of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN, USA.
Alexander G RabchevskySpinal Cord & Brain Injury, Research Center, University of Kentucky, Lexington, KY, USA.
Ronald B EmesonDepartment of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN, USA.
Stefan StammDepartment of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA stefan@stamms-lab.net.ORCID 0000-0002-9420-7912
University of Kentucky · USVanderbilt University · US

Funding

UNDERSTANDING THE MOLECULAR BASIS OF EPIGENETIC TRANSCRIPTIONAL SILENCINGP20RR020171 · NCRR · UNIVERSITY OF KENTUCKY · PI LOUIS HERSH, LOUIS HERSH LOUIS HERSH · 2004 to 2011
$16.5M
The role of IKKß in linking obesity to adipose tissue inflammation and adipogeneP20GM103527 · NIGMS · UNIVERSITY OF KENTUCKY · PI CASSIS, LISA A · 2012 to 2017
$13.7M
Stress-Mediated Alterations in Serotonin 2C Receptor Editing and FunctionP50MH096972 · NIMH · VANDERBILT UNIVERSITY · PI BLAKELY, RANDY D. · 2012 to 2016
$10.5M
Research Project: Sensory and Multisensory Contributions to AutismU54HD083211 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DYKENS, ELISABETH MAY · 2015 to 2019
$7.1M
Regulation of alternative pre-mRNA processing by small nucleolar RNAsR01GM083187 · NIGMS · UNIVERSITY OF KENTUCKY · PI STAMM, STEFAN · 2009 to 2012
$1.1M
Changing serotonin receptor 2C splice variants to combat spasticity after spinal cord injuryR21NS098186 · NINDS · UNIVERSITY OF KENTUCKY · PI RABCHEVSKY, ALEXANDER GEORGE, STAMM, STEFAN · 2017 to 2018
$414k
Preventing hyperphagia in Prader Willi syndrome using an oligonucleotideR21HD080035 · NICHD · UNIVERSITY OF KENTUCKY · PI STAMM, STEFAN · 2014 to 2015
$409k
NCRR NIH HHS P20 RR020171NICHD NIH HHS R21 HD080035NICHD NIH HHS U54 HD083211NIGMS NIH HHS P20 GM103527NIGMS NIH HHS R01 GM083187NIMH NIH HHS P50 MH096972NINDS NIH HHS R21 NS098186
6 · The paper itself

Abstract

The serotonin 2C receptor regulates food uptake, and its activity is regulated by alternative pre-mRNA splicing. Alternative exon skipping is predicted to generate a truncated receptor protein isoform, whose existence was confirmed with a new antiserum. The truncated receptor sequesters the full-length receptor in intracellular membranes. We developed an oligonucleotide that promotes exon inclusion, which increases the ratio of the full-length to truncated receptor protein. Decreasing the amount of truncated receptor results in the accumulation of full-length, constitutively active receptor at the cell surface. After injection into the third ventricle of mice, the oligonucleotide accumulates in the arcuate nucleus, where it changes alternative splicing of the serotonin 2C receptor and increases pro-opiomelanocortin expression. Oligonucleotide injection reduced food intake in both wild-type and ob/ob mice. Unexpectedly, the oligonucleotide crossed the blood-brain barrier and its systemic delivery reduced food intake in wild-type mice. The physiological effect of the oligonucleotide suggests that a truncated splice variant regulates the activity of the serotonin 2C receptor, indicating that therapies aimed to change pre-mRNA processing could be useful to treat hyperphagia, characteristic for disorders like Prader-Willi syndrome.

Indexed as

EatingAlternative SplicingAnimalsGene ExpressionGene Expression RegulationMiceOligonucleotidesPro-OpiomelanocortinProtein IsoformsReceptor, Serotonin, 5-HT2COligonucleotidesPro-OpiomelanocortinProtein IsoformsReceptor, Serotonin, 5-HT2Calternative splicingbrain functionfood uptakeobesitypre‐mRNA processing

Identifiers

PMID27406820
PMCPMC4967942
OpenAlexW2466404027

What OpenQuestion holds

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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.