Exon–Intron Differential Analysis Reveals the Role of Competing Endogenous RNAs in Post-Transcriptional Regulation of Translation
Stressful conditions induce the cell to save energy and activate a rescue program modulated by mammalian target of rapamycin (mTOR). Along with transcriptional and translational regulation, the cell relies also on post-transcriptional modulation to quickly adapt the translation of essential proteins...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
|
| Series: | Non-Coding RNA |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2311-553X/7/2/26 |
| _version_ | 1827694989073711104 |
|---|---|
| author | Nicolas Munz Luciano Cascione Luca Parmigiani Chiara Tarantelli Andrea Rinaldi Natasa Cmiljanovic Vladimir Cmiljanovic Rosalba Giugno Francesco Bertoni Sara Napoli |
| author_facet | Nicolas Munz Luciano Cascione Luca Parmigiani Chiara Tarantelli Andrea Rinaldi Natasa Cmiljanovic Vladimir Cmiljanovic Rosalba Giugno Francesco Bertoni Sara Napoli |
| author_sort | Nicolas Munz |
| collection | DOAJ |
| description | Stressful conditions induce the cell to save energy and activate a rescue program modulated by mammalian target of rapamycin (mTOR). Along with transcriptional and translational regulation, the cell relies also on post-transcriptional modulation to quickly adapt the translation of essential proteins. MicroRNAs play an important role in the regulation of protein translation, and their availability is tightly regulated by RNA competing mechanisms often mediated by long noncoding RNAs (lncRNAs). In our paper, we simulated the response to growth adverse condition by bimiralisib, a dual PI3K/mTOR inhibitor, in diffuse large B cell lymphoma cell lines, and we studied post-transcriptional regulation by the differential analysis of exonic and intronic RNA expression. In particular, we observed the upregulation of a lncRNA, lncTNK2-2:1, which correlated with the stabilization of transcripts involved in the regulation of translation and DNA damage after bimiralisib treatment. We identified miR-21-3p as miRNA likely sponged by lncTNK2-2:1, with consequent stabilization of the mRNA of p53, which is a master regulator of cell growth in response to DNA damage. |
| first_indexed | 2024-03-10T12:16:21Z |
| format | Article |
| id | doaj.art-5b5be392e2c347158754b46f11f2dfa0 |
| institution | Directory Open Access Journal |
| issn | 2311-553X |
| language | English |
| last_indexed | 2024-03-10T12:16:21Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Non-Coding RNA |
| spelling | doaj.art-5b5be392e2c347158754b46f11f2dfa02023-11-21T15:48:10ZengMDPI AGNon-Coding RNA2311-553X2021-04-01722610.3390/ncrna7020026Exon–Intron Differential Analysis Reveals the Role of Competing Endogenous RNAs in Post-Transcriptional Regulation of TranslationNicolas Munz0Luciano Cascione1Luca Parmigiani2Chiara Tarantelli3Andrea Rinaldi4Natasa Cmiljanovic5Vladimir Cmiljanovic6Rosalba Giugno7Francesco Bertoni8Sara Napoli9Institute of Oncology Research, Faculty of Biomedical Sciences, Universita`Svizzera Italiana, 6500 Bellinzona, SwitzerlandInstitute of Oncology Research, Faculty of Biomedical Sciences, Universita`Svizzera Italiana, 6500 Bellinzona, SwitzerlandComputer Science Department, University of Verona, 37129 Verona, ItalyInstitute of Oncology Research, Faculty of Biomedical Sciences, Universita`Svizzera Italiana, 6500 Bellinzona, SwitzerlandInstitute of Oncology Research, Faculty of Biomedical Sciences, Universita`Svizzera Italiana, 6500 Bellinzona, SwitzerlandPIQUR Therapeutics AG, 4057 Basel, SwitzerlandPIQUR Therapeutics AG, 4057 Basel, SwitzerlandComputer Science Department, University of Verona, 37129 Verona, ItalyInstitute of Oncology Research, Faculty of Biomedical Sciences, Universita`Svizzera Italiana, 6500 Bellinzona, SwitzerlandInstitute of Oncology Research, Faculty of Biomedical Sciences, Universita`Svizzera Italiana, 6500 Bellinzona, SwitzerlandStressful conditions induce the cell to save energy and activate a rescue program modulated by mammalian target of rapamycin (mTOR). Along with transcriptional and translational regulation, the cell relies also on post-transcriptional modulation to quickly adapt the translation of essential proteins. MicroRNAs play an important role in the regulation of protein translation, and their availability is tightly regulated by RNA competing mechanisms often mediated by long noncoding RNAs (lncRNAs). In our paper, we simulated the response to growth adverse condition by bimiralisib, a dual PI3K/mTOR inhibitor, in diffuse large B cell lymphoma cell lines, and we studied post-transcriptional regulation by the differential analysis of exonic and intronic RNA expression. In particular, we observed the upregulation of a lncRNA, lncTNK2-2:1, which correlated with the stabilization of transcripts involved in the regulation of translation and DNA damage after bimiralisib treatment. We identified miR-21-3p as miRNA likely sponged by lncTNK2-2:1, with consequent stabilization of the mRNA of p53, which is a master regulator of cell growth in response to DNA damage.https://www.mdpi.com/2311-553X/7/2/26miRNAslncRNAsceRNAstranslationpost-transcriptional regulationmTOR pathway |
| spellingShingle | Nicolas Munz Luciano Cascione Luca Parmigiani Chiara Tarantelli Andrea Rinaldi Natasa Cmiljanovic Vladimir Cmiljanovic Rosalba Giugno Francesco Bertoni Sara Napoli Exon–Intron Differential Analysis Reveals the Role of Competing Endogenous RNAs in Post-Transcriptional Regulation of Translation Non-Coding RNA miRNAs lncRNAs ceRNAs translation post-transcriptional regulation mTOR pathway |
| title | Exon–Intron Differential Analysis Reveals the Role of Competing Endogenous RNAs in Post-Transcriptional Regulation of Translation |
| title_full | Exon–Intron Differential Analysis Reveals the Role of Competing Endogenous RNAs in Post-Transcriptional Regulation of Translation |
| title_fullStr | Exon–Intron Differential Analysis Reveals the Role of Competing Endogenous RNAs in Post-Transcriptional Regulation of Translation |
| title_full_unstemmed | Exon–Intron Differential Analysis Reveals the Role of Competing Endogenous RNAs in Post-Transcriptional Regulation of Translation |
| title_short | Exon–Intron Differential Analysis Reveals the Role of Competing Endogenous RNAs in Post-Transcriptional Regulation of Translation |
| title_sort | exon intron differential analysis reveals the role of competing endogenous rnas in post transcriptional regulation of translation |
| topic | miRNAs lncRNAs ceRNAs translation post-transcriptional regulation mTOR pathway |
| url | https://www.mdpi.com/2311-553X/7/2/26 |
| work_keys_str_mv | AT nicolasmunz exonintrondifferentialanalysisrevealstheroleofcompetingendogenousrnasinposttranscriptionalregulationoftranslation AT lucianocascione exonintrondifferentialanalysisrevealstheroleofcompetingendogenousrnasinposttranscriptionalregulationoftranslation AT lucaparmigiani exonintrondifferentialanalysisrevealstheroleofcompetingendogenousrnasinposttranscriptionalregulationoftranslation AT chiaratarantelli exonintrondifferentialanalysisrevealstheroleofcompetingendogenousrnasinposttranscriptionalregulationoftranslation AT andrearinaldi exonintrondifferentialanalysisrevealstheroleofcompetingendogenousrnasinposttranscriptionalregulationoftranslation AT natasacmiljanovic exonintrondifferentialanalysisrevealstheroleofcompetingendogenousrnasinposttranscriptionalregulationoftranslation AT vladimircmiljanovic exonintrondifferentialanalysisrevealstheroleofcompetingendogenousrnasinposttranscriptionalregulationoftranslation AT rosalbagiugno exonintrondifferentialanalysisrevealstheroleofcompetingendogenousrnasinposttranscriptionalregulationoftranslation AT francescobertoni exonintrondifferentialanalysisrevealstheroleofcompetingendogenousrnasinposttranscriptionalregulationoftranslation AT saranapoli exonintrondifferentialanalysisrevealstheroleofcompetingendogenousrnasinposttranscriptionalregulationoftranslation |