Long non-coding RNA Neat1 and paraspeckle components are translational regulators in hypoxia

Archive ouverte

Godet, Anne-Claire | Roussel, Emilie | David, Florian | Hantelys, Fransky | Morfoisse, Florent | Alves, Joffrey | Pujol, Françoise | Ader, Isabelle | Bertrand, Edouard | Burlet-Schiltz, Odile | Froment, Carine | Henras, Anthony | Vitali, Patrice | Lacazette, Eric | Tatin, Florence | Garmy-Susini, Barbara | Prats, Anne-Catherine

Edité par CCSD ; eLife Sciences Publication -

International audience. 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 p54 nrb and PSPC1 as well as nucleolin and RPS2, two p54 nrb -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.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion