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  A long non-coding RNA links calreticulin-mediated immunogenic cell removal to RB1 transcription

Musahl, A., Huang, X., Rusakiewicz, S., Ntini, E., Marsico, A., Kroemer, G., et al. (2015). A long non-coding RNA links calreticulin-mediated immunogenic cell removal to RB1 transcription. Oncogene, 34(39), 5046-5054. doi:10.1038/onc.2014.424.

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 Creators:
Musahl, A.1, Author              
Huang, X., Author
Rusakiewicz, S., Author
Ntini, E.1, Author
Marsico, A.2, Author              
Kroemer, G., Author
Kepp, O., Author
Ørom, U. A.1, Author              
Affiliations:
1Long non-coding RNA (Ulf Andersson Ørom), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479659              
2RNA Bioinformatics (Annalisa Marsico), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2117285              

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 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.

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Language(s): eng - English
 Dates: 2015-01-122015-09-24
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1038/onc.2014.424
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Title: Oncogene
Source Genre: Journal
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Publ. Info: Basingstoke, Hampshire, UK : Scientific & Medical Division, Macmillan Press
Pages: - Volume / Issue: 34 (39) Sequence Number: - Start / End Page: 5046 - 5054 Identifier: ISSN: 0950-9232
CoNE: https://pure.mpg.de/cone/journals/resource/954925574955