PT  - JOURNAL ARTICLE
AU  - Anne-Claire Godet
AU  - Florian David
AU  - Emilie Roussel
AU  - Fransky Hantelys
AU  - Florent Morfoisse
AU  - Joffrey Alves
AU  - Françoise Pujol
AU  - Isabelle Ader
AU  - Edouard Bertrand
AU  - Odile Burlet-Schiltz
AU  - Carine Froment
AU  - Anthony K. Henras
AU  - Patrice Vitali
AU  - Eric Lacazette
AU  - Florence Tatin
AU  - Barbara Garmy-Susini
AU  - Anne-Catherine Prats
TI  - Long non-coding RNA Neat1 is a key translational regulator in hypoxia
AID  - 10.1101/2021.02.10.430272
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.02.10.430272
4099  - http://biorxiv.org/content/early/2021/02/10/2021.02.10.430272.short
4100  - http://biorxiv.org/content/early/2021/02/10/2021.02.10.430272.full
AB  - 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 shows that the Neat1_2 isoform widely affects translation of mRNAs containing IRESs, involved in stress response, angiogenesis or cardioprotection.HighlightsInduction of lncRNA Neat1 and paraspeckle formation correlates with activation of IRES-dependent translation in hypoxic cardiomyocytes.Neat1, an essential paraspeckle component, is the key IRES trans-acting factor (ITAF) of (lymph)angiogenic and cardioprotective factor mRNA IRESs.Paraspeckle proteins p54nrb and PSPC1 as well as nucleolin and Rps2, two p54nrb-interacting proteins, are ITAFs of IRES subgroups.Paraspeckle appears as a platform for IRESome formation in nucleus.The Neat1_2 isoform plays a pivotal role in translation of mRNA containing IRESs and of genes involved in the stress response.Competing Interest StatementThe authors have declared no competing interest.