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.