![]() Furthermore, recent reports have suggested that vtRNA may function to regulate cellular pathophysiology. The number of vtRNA paralogs differs among species: humans express four (vtRNA1-1, vtRNA1-2, vtRNA1-3, and vtRNA2-1), while mice express only one. In addition to the vtRNAs, the vault complex consists of multiple copies of three protein species: the major vault protein (MVP), the vault poly(ADP-ribose)-polymerase, and telomerase-associated protein 1 ( Berger et al., 2009). Small noncoding vault RNAs (vtRNAs) have been described as a component of the vault complex, a hollow, barrel-shaped ribonucleoprotein complex found in most eukaryotes ( Kedersha and Rome, 1986 Stadler et al., 2009). Roles of ncRNAs were first characterized in protein synthesis as ribosomes or transfer RNAs, and subsequently a number of additional functions have been identified, including transcription, translation, RNA processing, and chromatin remodeling, and they also contribute to protein stability and localization ( Amaral et al., 2008 Gebetsberger and Polacek, 2013 Hüttenhofer et al., 2005 Sabin et al., 2013 Tuck and Tollervey, 2011). ![]() ![]() Noncoding RNAs (ncRNAs) function at the RNA level and are not translated into proteins. Unfortunately, the precise molecular mechanism for these regulations remains elusive. Among such kinases, the MAPK signaling pathway leading to the activation of extracellular signal-regulated kinase 1 and 2 (ERK1 and ERK2) plays a key role in regulating local protein synthesis in dendrites, formation and stabilization of dendritic spines, and synaptic plasticity in the brain ( Sweatt, 2004 Thomas and Huganir, 2004). Subcellular signaling, involving protein kinases, plays a significant role in the establishment and regulation of neuronal connectivity at synapses. Neurodevelopmental disorders, including autism spectrum disorders, are characterized at cellular levels by abnormal establishment of neuronal connectivity during development ( Gilbert and Man, 2017 Mohammad-Rezazadeh et al., 2016). The establishment of axon/dendrite polarity is a critical step in neuronal differentiation ( Barnes and Polleux, 2009 Yogev and Shen, 2017). These results suggest the existence of a regulatory mechanism of the MAPK signaling pathway by vtRNAs as a new molecular basis for synapse formation. mvtRNA binds to and activates MEK1 and thereby enhances MEK1-mediated ERK activation in neurites. Interestingly, mvtRNA is released from the vault complex in the neurite by a mitotic kinase Aurora-A–dependent phosphorylation of MVP, a major protein component of the vault complex. mvtRNA is transported to the distal region of neurites as part of the vault complex. Using an in vitro synapse formation model, we show that murine vtRNA (mvtRNA) promotes synapse formation by modulating the MAPK signaling pathway. Here, we demonstrate a novel role for vtRNA in synaptogenesis. Emerging evidence suggests that vtRNAs may be involved in the regulation of a variety of cellular functions when unassociated with the vault complex. The small noncoding vault RNA (vtRNA) is a component of the vault complex, a ribonucleoprotein complex found in most eukaryotes.
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