Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

U1 snRNP suppresses microRNA biogenesis by alternative intronic polyadenylation in melanoma

Sandra Vorlova, Gina Blahetek, Ruggero Barbieri, Yvonne Kerstan, Annabelle Rosa, Maja Bundalo, Manuel Egg, Elke Butt, Erik Henke, Lars Dölken, Roland Houben, Bastian Schilling, Utz Fischer, Florian Erhard, Alma Zernecke
doi: https://doi.org/10.1101/2022.06.01.479622
Sandra Vorlova
1Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gina Blahetek
1Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ruggero Barbieri
1Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yvonne Kerstan
1Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Annabelle Rosa
1Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maja Bundalo
1Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Manuel Egg
1Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elke Butt
1Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erik Henke
2Institute of Anatomy and Cell Biology, Julius-Maximilians-University, Würzburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lars Dölken
3Institute for Virology and Immunobiology, Julius-Maximilians-University, Würzburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roland Houben
4Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bastian Schilling
4Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Utz Fischer
5Department of Biochemistry, Theodor Boveri Institute, Julius-Maximilians-University, Würzburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Florian Erhard
3Institute for Virology and Immunobiology, Julius-Maximilians-University, Würzburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alma Zernecke
1Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: alma.zernecke@uni-wuerzburg.de
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Activation of intronic polyadenylation signals results in premature cleavage and polyadenylation (PCPA). The majority of mammalian miRNAs are also located within intronic regions of protein-coding genes and are transcriptionally co-expressed with their host genes. Here we show that U1-dependent PCPA by telescripting dysregulates miRNA biogenesis. When U1 is reduced, miR-211 levels are decreased as a direct consequence of activation of a newly identified alternative intronic polyadenylation signal located upstream of miR-211 within its host gene TRPM1. Various melanoma cell lines revealed decreased U1 levels and a shift from full-length to truncated TRPM1 isoforms with concomitant decreased miR-211 expression. Modulation of TRPM1 alternative polyadenylation (APA) by morpholino oligonucleotides inhibits and potentially restores miR-211 expression to endogenous levels. This mechanism of intronic PCPA and its effects on miRNA biogenesis represents a previously unrecognized layer of gene expression regulation suitable for therapeutic modulation.

Figure
  • Download figure
  • Open in new tab

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted June 01, 2022.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
U1 snRNP suppresses microRNA biogenesis by alternative intronic polyadenylation in melanoma
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
U1 snRNP suppresses microRNA biogenesis by alternative intronic polyadenylation in melanoma
Sandra Vorlova, Gina Blahetek, Ruggero Barbieri, Yvonne Kerstan, Annabelle Rosa, Maja Bundalo, Manuel Egg, Elke Butt, Erik Henke, Lars Dölken, Roland Houben, Bastian Schilling, Utz Fischer, Florian Erhard, Alma Zernecke
bioRxiv 2022.06.01.479622; doi: https://doi.org/10.1101/2022.06.01.479622
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
U1 snRNP suppresses microRNA biogenesis by alternative intronic polyadenylation in melanoma
Sandra Vorlova, Gina Blahetek, Ruggero Barbieri, Yvonne Kerstan, Annabelle Rosa, Maja Bundalo, Manuel Egg, Elke Butt, Erik Henke, Lars Dölken, Roland Houben, Bastian Schilling, Utz Fischer, Florian Erhard, Alma Zernecke
bioRxiv 2022.06.01.479622; doi: https://doi.org/10.1101/2022.06.01.479622

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Molecular Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4688)
  • Biochemistry (10379)
  • Bioengineering (7695)
  • Bioinformatics (26372)
  • Biophysics (13547)
  • Cancer Biology (10720)
  • Cell Biology (15460)
  • Clinical Trials (138)
  • Developmental Biology (8509)
  • Ecology (12842)
  • Epidemiology (2067)
  • Evolutionary Biology (16885)
  • Genetics (11416)
  • Genomics (15493)
  • Immunology (10638)
  • Microbiology (25254)
  • Molecular Biology (10239)
  • Neuroscience (54587)
  • Paleontology (402)
  • Pathology (1671)
  • Pharmacology and Toxicology (2899)
  • Physiology (4355)
  • Plant Biology (9263)
  • Scientific Communication and Education (1588)
  • Synthetic Biology (2561)
  • Systems Biology (6789)
  • Zoology (1470)