Long non-coding RNA Neat1 and paraspeckle components are translational regulators in hypoxia
- Inserm UMR 1297, France
- Inserm, UMR 1301, France
- Institut de Génétique Moléculaire de Montpellier, France
- CNRS, France
- CNRS, Université Paul Sabatier, France
Abstract
Internal ribosome entry sites (IRESs) drive translation initiation during stress. In response to hypoxia, (lymph)angiogenic factors responsible for tissue revascularization in ischemic diseases are induced by the IRES-dependent mechanism. Here we searched for IRES trans-acting factors (ITAFs) active in early hypoxia in mouse cardiomyocytes. Using knock-down and proteomics approaches, we show a link between a stressed-induced nuclear body, the paraspeckle, and IRES-dependent translation. Furthermore, smiFISH experiments demonstrate the recruitment of IRES-containing mRNA into paraspeckle during hypoxia. Our data reveal that the long non-coding RNA Neat1, an essential paraspeckle component, is a key translational regulator, active on IRESs of (lymph)angiogenic and cardioprotective factor mRNAs. In addition, paraspeckle proteins p54nrb and PSPC1 as well as nucleolin and RPS2, two p54nrb-interacting proteins identified by mass spectrometry, are ITAFs for IRES subgroups. Paraspeckle thus appears as a platform to recruit IRES-containing mRNAs and possibly host IRESome assembly. Polysome PCR array shows that Neat1 isoforms regulate IRES-dependent translation and, more widely, translation of mRNAs involved in stress response.
Data availability
Lentivector plasmid sequences are available on Dryad. https://doi.org/10.5061/dryad.2330r1band doi:10.5061/dryad.m0cfxpp75.The MS proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD024067.
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Long non-coding RNA Neat1 and paraspeckle components are translational regulators in hypoxiaDryad Digital Repository, doi:10.5061/dryad.m0cfxpp75.
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Data from: Vasohibin1, a new IRES trans-acting factor for induction of (lymph)angiogenic factors in early hypoxiaDryad Digital Repository, doi:10.5061/dryad.2330r1b.
Article and author information
Author details
Anne-Catherine Prats
Funding
Agence Nationale de la Recherche (ANR-18-CE11-0020-RIBOCARD)
- Anne-Catherine Prats
Agence Nationale de la Recherche (ProFI ANR-10-INBS-08)
- Odile Burlet-Schiltz
- Carine Froment
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Godet et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Long non-coding RNA Neat1 and paraspeckle components are translational regulators in hypoxia
eLife 11:e69162.
https://doi.org/10.7554/eLife.69162
Further reading
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