A circular RNA derived from the Tulp4 gene controls excitatory neurotransmission and regulates anxiety-related behavior

GIULIANA C DI MAURO; FLORENCIA MERINO; SEBASTIAN GIUSTI; NATALIA PINO; MORA OGANDO; BELÉN PARDI; ANONIA MARIN BURGIN; OLAF JAHN; NILS BROSE; WOLFGANG WURST; DAMIAN REFOJO

Villa Carlos Paz

Congreso; Sociedad Argentina de Investigación en Neurociencias; 2019

Exonic circular RNAs (circRNAs) are a recently characterized class of noncoding RNAs. Thesemolecules 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 circulartranscripts derived from nerve tissue samples. From these data, we have selected a circular RNAtranscript derived from the Tulp4 (Tubby-like protein 4) gene to perform a functionalcharacterization. We observed in loss-of-function experiments, both in primary neurons and in brainslices, 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, have changes in the protein composition of synaptic compartments and exhibit behavioral alterations including working-memory deficits and increased anxiety.