title: A long non-coding RNA links calreticulin-mediated immunogenic cell removal to RB1 transcription.
abstract: A subset of promoters bidirectionally expresses long non-coding RNAs (ncRNAs) of unknown function and protein-coding genes (PCGs) in parallel. Here, we define a set of 1107 highly conserved human bidirectional promoters that mediate the linked expression of long ncRNAs and PCGs. Depletion of the long ncRNA expressed from the RB1 promoter, ncRNA-RB1, reveals regulatory effects different from the RB1-controlled transcriptional program. ncRNA-RB1 positively regulates the expression of calreticulin (CALR) that in response to certain therapeutic interventions can translocate from the endoplasmic reticulum to the cell surface, hence activating anticancer immune responses. Knockdown of ncRNA-RB1 in tumor cells reduced expression of CALR, impaired the translocation of the protein to the cell surface upon treatment with anthracylines and consequently inhibited the cellular uptake by macrophages. In conclusion, co-transcription of ncRNA-RB1 and RB1 provides a positive link between the expression of the two tumor suppressors RB1 and the immune-relevant CALR protein. This regulatory interplay exemplifies disease-relevant co-regulation of two distinct gene products, in which loss of expression of one oncosuppressor protein entails the abolition of additional tumor-inhibitory mechanisms.
authors.affiliation: Noncoding RNA Research Group, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: A-S
authors.initials: AS
authors.lastname: Musahl
authors.affiliation: Team11, Equipe labellisée Ligue contre le Cancer, INSERM U1138, Cordeliers Research Cancer, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Cell Biology and Metabolomics Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France.
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.affiliation: Gustave Roussy, Villejuif, France.|INSERM, U1015; CICBT507, Villejuif, France.
authors.forename: S
authors.initials: S
authors.lastname: Rusakiewicz
authors.affiliation: Noncoding RNA Research Group, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Ntini
authors.affiliation: Department of Computational Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.|RNA Bioinformatics group, Max Planck Institute for Molecular Genetics, Berlin, Germany.|Free University of Berlin, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Marsico
authors.affiliation: Team11, Equipe labellisée Ligue contre le Cancer, INSERM U1138, Cordeliers Research Cancer, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Cell Biology and Metabolomics Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France.|Université Pierre et Marie Curie, Paris, France.|Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Kroemer
authors.affiliation: Team11, Equipe labellisée Ligue contre le Cancer, INSERM U1138, Cordeliers Research Cancer, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Cell Biology and Metabolomics Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France.
authors.forename: O
authors.initials: O
authors.lastname: Kepp
authors.affiliation: Noncoding RNA Research Group, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: U A
authors.initials: UA
authors.lastname: Ørom
mesh_terms: D037282:Calreticulin / Q000378:metabolism*; D002460:Cell Line; D016161:Genes, Retinoblastoma; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D037282:Calreticulin; D062085:RNA, Long Noncoding