Ricerc@Sapienza

Circular RNAs (circRNAs) represent an emerging class of non-coding RNA molecules, evolutionarily conserved and highly enriched in the mammalian nervous systems. Their expression is dynamically regulated during neurodevelopment, neuronal differentiation, and synaptic plasticity events, suggesting a potential involvement in these processes. They act as regulators of gene expression both at the transcriptional and posttranscriptional level by interacting with proteins and microRNAs. In our previous work, we identified and validated several circRNAs differentially expressed in the hippocampus of the BTBR mouse model for autism spectrum disorder (ASD) [1]. We characterized the ASD-related circRmst, identifying its tight regulation during pre- and post-natal mouse brain development and neuronal differentiation. In addition, to shed light on circRmst biological function, by in silico analysis and RIP experiments, we investigated its putative interaction with SOX2, one of the most important transcription factors controlling neural stem cell fate and differentiation [2]. We aim to better characterize the role of circRmst in neurogenesis, exploring features and potential functional implications of its molecular interaction with SOX2 and investigating the outcome of this crosstalk. To address those issues, experiments of co-localization and reverse genetics will be performed in in vitro differentiated neuronal cells and primary neurons. Moreover, circRmst/Sox2 interaction will be analyzed in pathological contexts, such as in the ASD mouse model in which we detected significantly altered levels of circRmst.
[1] S. Gasparini, V. Licursi, C. Presutti, and C. Mannironi, ¿The Secret Garden of Neuronal circRNAs,¿ Cells, vol. 9, no. 8, Jul. 2020, doi: 10.3390/CELLS9081815.
[2] B.-Y. M et al., ¿Role of Sox2 in the development of the mouse neocortex,¿ Dev. Biol., vol. 295, no. 1, pp. 52¿66, Jul. 2006, doi: 10.1016/J.YDBIO.2006.03.007.