Manara - Qatar Research Repository
Browse
Post-transcriptional_regulation_of_Pabpn1_by_the_R.pdf (4.16 MB)

Post-transcriptional regulation of Pabpn1 by the RNA binding protein HuR

Download (4.16 MB)
journal contribution
submitted on 2024-05-30, 10:29 and posted on 2024-05-30, 10:29 authored by Brittany L Phillips, Ayan Banerjee, Brenda J Sanchez, Sergio Di Marco, Imed-Eddine Gallouzi, Grace K Pavlath, Anita H Corbett

RNA processing is critical for proper spatial and temporal control of gene expression. The ubiquitous nuclear polyadenosine RNA binding protein, PABPN1, post-transcriptionally regulates multiple steps of gene expression. Mutations in the PABPN1 gene expanding an N-terminal alanine tract in the PABPN1 protein from 10 alanines to 11-18 alanines cause the muscle-specific disease oculopharyngeal muscular dystrophy (OPMD), which affects eyelid, pharynx, and proximal limb muscles. Previous work revealed that the Pabpn1 transcript is unstable, contributing to low steady-state Pabpn1 mRNA and protein levels in vivo, specifically in skeletal muscle, with even lower levels in muscles affected in OPMD. Thus, low levels of PABPN1 protein could predispose specific tissues to pathology in OPMD. However, no studies have defined the mechanisms that regulate Pabpn1 expression. Here, we define multiple cis-regulatory elements and a trans-acting factor, HuR, which regulate Pabpn1 expression specifically in mature muscle in vitro and in vivo. We exploit multiple models including C2C12 myotubes, primary muscle cells, and mice to determine that HuR decreases Pabpn1 expression. Overall, we have uncovered a mechanism in mature muscle that negatively regulates Pabpn1 expression in vitro and in vivo, which could provide insight to future studies investigating therapeutic strategies for OPMD treatment.

Other Information

Published in: Nucleic Acids Research
License: http://creativecommons.org/licenses/by-nc/4.0/
See article on publisher's website: https://dx.doi.org/10.1093/nar/gky535

Funding

Open Access funding provided by the Qatar National Library.

History

Language

  • English

Publisher

Oxford University Press

Publication Year

  • 2018

License statement

This Item is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Science and Engineering - HBKU

Usage metrics

    College of Science and Engineering - HBKU

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC