CircTulp4: A circular RNA that controls excitatory neurotransmission

MERINO, FLORENCIA L.; GIUSTI, SEBASTIÁN A.; NATALIA S. PINO; MORA OGANDO; PARDI, BELÉN; ANTONIA MARIN-BURGIN; WURST, WOLFGANG; REFOJO, DAMIÁN

Córdoba

Congreso; XXXIII Congreso de la Sociedad Argentina de Neurociencias; 2018

Sociedad Argentina de Neurociencias

Exonic circular RNAs (circRNAs) are a recently characterized class of noncoding RNAs. These molecules derive from exonic sequences and are generated by an alternative mechanism of splicing known as backsplicing, which yields a single-stranded RNA molecule with covalently joined ends. Due to their recent identification, the function of circRNAs is still almost unexplored.We have recently accomplished a systematic high throughput identification of numerous circular transcripts derived from nerve tissue samples. From these data, we have selected a circular RNA transcript derived from the Tulp4 (Tubby-like protein 4) gene to perform a functional characterization. We observed in loss-of-function experiments, both in primary neurons and in brain slices, that circTulp4 regulates excitatory neurotransmission and affects the number of glutamatergic synaptic contacts.To study the role of circTulp4 in vivo, we have generated a transgenic knock-out mouse line mutating a splicing acceptor site using CRISPR/Cas9 technique. Preliminary results show that mice lacking circTulp4 have impaired neurotransmission and exhibit memory deficits.