Rn7SK small nuclear RNA is involved in neuronal differentiation

Abstract

Rn7SK-mediated global transcriptional regulation, key function of this small nuclear RNA (snRNA), is mediated by inhibition of the positive transcription elongation factor b (P-TEFb). Recently, we have identified a potential anti-proliferative and tumor-suppressive function of Rn7SK. However, its possible regulatory role in development and cell programming has not been investigated so far. Here, we examined transcriptional levels of Rn7SK in different mouse organs. Interestingly, an increased expression level of the RNA was observed in the brain. Furthermore, we could demonstrate that Rn7SK has a dynamic expression pattern during brain development from embryo to adult: 7SK snRNA expression was particularly high at embryonic day (E) 18.5 and adult stages, while a low level of this non-coding RNA was detected at E11.5. Moreover, a decreased transcription level was identified in proliferating progenitors whereas a strong upregulation of Rn7SK was observed during neural differentiation in vivo. Similar to the in vivo situation, in vitro neuronal differentiation experiments employing embryonic stem cells (ESCs) demonstrated the same expression pattern of 7SK with high expression levels in differentiating neurons. Neuronal differentiation of ESCs was compromised when we knocked down Rn7SK, indicating an important role of 7SK in the acquisition of a neural fate.

Keywords: P-TEFb; Rn7SK; brain; neural differentiation; non-coding RNA; snRNP complex; stem cells.