Long non-coding RNA Neat1 is a key of translational regulator in hypoxia

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. 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 the site of IRESome assembly in the nucleus. Polysome PCR array showed that the Neat1_2 isoform widely affects translation of mRNAs containing IRESs, involved in stress response, angiogenesis or cardioprotection.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Cardiac Muscle Cell

DISEASE(S): Myocardial Ischemia

SUBMITTER: Carine Froment  

LAB HEAD: Anne-Catherine Prats

PROVIDER: PXD024067 | Pride | 2023-01-03

REPOSITORIES: Pride