title: Long noncoding RNA PANDA and scaffold-attachment-factor SAFA control senescence entry and exit.
abstract: Cellular senescence is a stable cell cycle arrest that limits the proliferation of pre-cancerous cells. Here we demonstrate that scaffold-attachment-factor A (SAFA) and the long noncoding RNA PANDA differentially interact with polycomb repressive complexes (PRC1 and PRC2) and the transcription factor NF-YA to either promote or suppress senescence. In proliferating cells, SAFA and PANDA recruit PRC complexes to repress the transcription of senescence-promoting genes. Conversely, the loss of SAFA-PANDA-PRC interactions allows expression of the senescence programme. Accordingly, we find that depleting either SAFA or PANDA in proliferating cells induces senescence. However, in senescent cells where PANDA sequesters transcription factor NF-YA and limits the expression of NF-YA-E2F-coregulated proliferation-promoting genes, PANDA depletion leads to an exit from senescence. Together, our results demonstrate that PANDA confines cells to their existing proliferative state and that modulating its level of expression can cause entry or exit from senescence.
authors.affiliation: 1] Department of Pediatrics, University of Utah, Salt Lake City, Utah 84102, USA [2] Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822, USA.
authors.forename: Pavan Kumar
authors.initials: PK
authors.lastname: Puvvula
authors.affiliation: Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822, USA.
authors.forename: Rohini Devi
authors.initials: RD
authors.lastname: Desetty
authors.affiliation: 1] Institut Pasteur, Laboratory of Nuclear Organization and Oncogenesis, F-75015 Paris, France [2] INSERM, U993, F-75015 Paris, France [3] Equipe Labellisée Ligue Nationale Contre le Cancer, F-75015 Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pineau
authors.affiliation: 1] Institut Pasteur, Laboratory of Nuclear Organization and Oncogenesis, F-75015 Paris, France [2] INSERM, U993, F-75015 Paris, France [3] Equipe Labellisée Ligue Nationale Contre le Cancer, F-75015 Paris, France.
authors.forename: Agnés
authors.initials: A
authors.lastname: Marchio
authors.affiliation: 1] Department of Pediatrics, University of Utah, Salt Lake City, Utah 84102, USA [2] Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Moon
authors.affiliation: 1] Institut Pasteur, Laboratory of Nuclear Organization and Oncogenesis, F-75015 Paris, France [2] INSERM, U993, F-75015 Paris, France [3] Equipe Labellisée Ligue Nationale Contre le Cancer, F-75015 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Dejean
authors.affiliation: 1] Institut Pasteur, Laboratory of Nuclear Organization and Oncogenesis, F-75015 Paris, France [2] INSERM, U993, F-75015 Paris, France.
authors.forename: Oliver
authors.initials: O
authors.lastname: Bischof
mesh_terms: D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics*; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D034722:Heterogeneous-Nuclear Ribonucleoprotein U / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism
chemical_list: D023081:CCAAT-Binding Factor; D018797:Cell Cycle Proteins; D050684:E2F Transcription Factors; D034722:Heterogeneous-Nuclear Ribonucleoprotein U; C492061:NFYA protein, human; C116662:PRC1 protein, human; D062085:RNA, Long Noncoding; D063151:Polycomb Repressive Complex 2