17A, a novel non-coding RNA, regulates GABA B alternative splicing and signaling in response to inflammatory stimuli and in Alzheimer disease
| Autor: | Elena Gatta, Claudio Russo, Roberta Borghi, Irene Vassallo, Sara Massone, Tullio Florio, Giorgio Dieci, Aldo Pagano, Mauro Robello, Federica Barbieri, Ranieri Cancedda, Gloria Fiorino, Manuele Castelnuovo, Massimo Tabaton |
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| Rok vydání: | 2010 |
| Předmět: |
Gene isoform
RNA Untranslated Molecular Sequence Data Amyloid beta KeyWords Plus:HUMAN NEUROBLASTOMA-CELLS Biology RNA polymerase III lcsh:RC321-571 CULTURE Downregulation and upregulation Author Keywords:RNA polymerase III Neurodegeneration Inflammation POLYMERASE-III RECEPTOR TRANSCRIPTOME Alzheimer Disease Cell Line Tumor medicine Humans Gene lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Base Sequence Alternative splicing RNA RNA Polymerase III Amyloid β medicine.disease Non-coding RNA Receptors GABA-A Molecular biology Cell biology Up-Regulation Alternative Splicing Neurology RNA Long Noncoding Inflammation Mediators HeLa Cells Signal Transduction |
| Zdroj: | Neurobiology of Disease, Vol 41, Iss 2, Pp 308-317 (2011) |
| ISSN: | 1095-953X |
| Popis: | Alternative splicing is a central component of human brain complexity; nonetheless, its regulatory mechanisms are still largely unclear. In this work, we describe a novel non-coding (nc) RNA (named 17A) RNA polymerase (pol) III-dependent embedded in the human G-protein-coupled receptor 51 gene (GPR51, GABA B2 receptor). The stable expression of 17A in SHSY5Y neuroblastoma cells induces the synthesis of an alternative splicing isoform that abolish GABA B2 intracellular signaling (i.e., inhibition of cAMP accumulation and activation of K(+) channels). Indeed, 17A is expressed in human brain, and we report that it is upregulated in cerebral tissues derived from Alzheimer disease patients. We demonstrate that 17A expression in neuroblastoma cells enhances the secretion of amyloid β peptide (Aβ) and the Aβ x-42/Αβ x-40 peptide ratio and that its synthesis is induced in response to inflammatory stimuli. These data correlate, for the first time, the activity of a novel pol III-dependent ncRNA to alternative splicing events and, possibly, to neurodegeneration induced by abnormal GABA B function. We anticipate that further analysis of pol III-dependent regulation of alternative splicing will disclose novel regulatory pathways associated to brain physiology and/or pathology. |
| Databáze: | OpenAIRE |
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