CircTulp4: a circular RNA that regulates working memory, anxiety and reward-related behavior in mice

GIUSTI, SEBASTIÁN A.; PARDI, BELÉN; BROSE, NILS; GIMENO, MARÍA LAURA; MORA OGANDO; JAHN, OLAF; DAMIAN REFOJO; PANNUNZIO, CAMILA; NATALIA S. PINO; ANTONIA MARIN-BURGIN; WURST, WOLFGANG

modalidad virtual

Congreso; XXXV Reunión Anual Sociedad Argentina de Neurociencias 2020; 2020

Sociedad Argentina de Neurociencias

Circular RNAs (circRNAs) are a newly characterized class of noncodingRNAs. These molecules derive from exonic sequences and are the products of analternative mechanism of splicing known as backsplicing, which yields asingle-stranded RNA molecule with covalently joined ends. Using a systematichigh throughput identification of numerous circular transcripts in nerve tissuesamples, we have selected a circular RNA transcript derived from the Tulp4(Tubby-like protein 4) gene to perform a functional characterization, based onits high expression level and its synaptic enrichment.We have recently generated a transgenic knock-out mouse line to modelcircTulp4 loss-of-function in vivo.To do so, we used the CRISPR/Cas9 technique to mutate the splicing acceptorsite used in the backsplice reaction. Electrophysiological and proteomicexperiments demonstrate that circTulp4 KO mice have alterations in theexcitatory neurotransmission and exhibit modified levels of synaptic proteins.More recently, we performed a microscopic quantitative analysis of brainsections having a sparse population of genetically labelled neurons expressingEGFP. The results show that mice lacking circTulp4 have an increased number ofdendritic spines. Notably, extensive behavioral phenotyping of circTulp4 KOmice suggests that circTulp4 affects specific aspects of different behaviorsincluding cognition, anxiety and reward.