Non-protein-producing RNA molecules, known as non-coding RNA molecules, have been described in the last decade of research as crucial for modulating the expression of information contained in genes and the processes that determine the development of different tissues and organs, including the nervous system. Their unique characteristic of acting on individual tissues in specific ways and at precise moments in cell development and differentiation makes this class of molecules extremely interesting in biomedical research.

In a recent study co-ordinated by Sapienza University of Rome and the Italian Institute of Technology (IIT in Italian), and funded by an ERC-Synergy project, a new long non-coding RNA (lncRNA) molecule, called CyCoNP, was discovered and the mechanism by which it regulates the branching of neural extensions (neurites) responsible for the transmission and reception of nerve impulses was described. The results of the work, published in the journal Nucleic Acids Research, confirm the role of non-coding RNAs in the control of neuronal homeostasis, thus expanding the list of possible targets and therapeutic approaches for the treatment of neurological diseases.

The researchers, coordinated by Irene Bozzoni of the Charles Darwin Department of Biology and Biotechnology of Sapienza University of Rome and IIT's CLN2S centre, have characterised the molecular and biological mechanism by which this lncRNA acts. Specifically, it was found that CyCoNP is very abundant in human motor neurons, particularly in the early differentiation phase where neural progenitor stage cells are numerous. In these cells, lncRNA specifically regulates the expression levels of NCAM1, a protein crucial for neuronal function and especially for regulating neurite branching. The researchers were able to dissect in detail the mechanism of action of CyCoNP, which involves the physical interaction between lncRNA, the messenger RNA that enables NCAM1 production, and a microRNA that is able to target both molecules.

The work, which describes a hitherto uncharacterised mechanism of action for non-coding RNAs, contributes significantly to expanding our knowledge of how this heterogeneous class of molecules functions and how they may play a key role in vital processes in our cells, such as the regulation of nerve signal transmission.

Keeping the focus on studying the multiple modes of action of non-coding RNAs is crucial to elucidating new mechanisms by which RNA functions in specific biological processes.

References:

CyCoNP lncRNA establishes cis and trans RNA-RNA interactions to supervise neuron physiology - Desideri F, Grazzi A, Lisi M et al. Nucleic Acids Research 2024 https://doi.org/10.1093/nar/gkae590

Further Information

Irene Bozzoni
Department of Biology and Biotechnology Charles Darwin
irene.bozzoni@uniroma1.it