Human vault RNA1-1, but not vault RNA2-1, modulates synaptogenesis

The small non-coding vault RNA (vtRNA) is a component of the vault complex, a ribonucleoprotein complex found in most eukaryotes. vtRNAs regulate a variety of cellular functions when unassociated with the vault complex. Human has four vtRNA paralogs (hvtRNA1-1, hvtRNA1-2, hvtRNA1-3, hvtRNA2-1), which are highly similar and differ only slightly in primary and secondary structure. Despite the increasing research on vtRNAs, a feature that distinguishes one hvtRNA from the others has not been recognized. Recently, we demonstrated that murine vtRNA (mvtRNA) promotes synapse formation by modulating the MAPK signaling pathway. Here we showed that expression ofhvtRNA1-1, but not hvtRNA2-1 increases the expression of synaptic marker proteins, ERK phosphorylation and the number of PSD95 and Synapsin I double positive puncta to an extent similar to that of mvtRNA, suggesting that hvtRNA1-1 may enhance synapse formation. This finding opens new perspectives to uncover the function of the different vtRNA paralogs.