Understanding determinants and functions of MATR3 binding along HSCHARME intronic sequence

Tissue-specific long non-coding RNAs (lncRNA) play pivotal roles in cellular physiology and differentiation, although the knowledge of their mechanisms of action remains largely elusive. In particular, their ability to interact with RNA-binding proteins (RBPs) enables them to coordinate crucial cellular functions. Furthermore, this interaction also drives the formation of some subcellular compartmentalisations. The murine lncRNA Charme is a highly conserved and abundant lncRNA specifically expressed in the nucleus of differentiated myotubes, whose ablation causes myogenic defects [1], [2]. Notably, its nuclear isoform, pCharme, is functional thanks to its retained intron, which mediates interactions with Matr3 and Ptbp1 [2], [3]. We are currently investigating the function of its human synthenic transcript, HSCHARME, which conserves its muscle-specific expression pattern and appears to play a critical role during human myogenesis. In particular, we are focusing on defining MATR3 binding modules along the HSCHARME intron 1, which spans over 12 kb in length, and on understanding the structural determinants underlying this interaction. Finally, the strong binding affinity of MATR3 for this region could offer a promising strategy for the design of RNA-based aptamers aimed at detecting MATR3 aggregates or targeting them therapeutically in ALS and other neuromuscular diseases involving MATR3.