Long non-coding RNA Neat1 and paraspeckle components are translational regulators in hypoxia
Cite this dataset
Prats, Anne-Catherine et al. (2022). Long non-coding RNA Neat1 and paraspeckle components are translational regulators in hypoxia [Dataset]. Dryad. https://doi.org/10.5061/dryad.m0cfxpp75
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.
Agence Nationale de la Recherche, Award: ANR-18-CE11-0020-RIBOCARD
Agence Nationale de la Recherche, Award: ProFI ANR-10-INBS-08