Novel ncRNAs transcribed by Pol III and elucidation of their functional relevance by biophysical approaches.

Paola Gavazzo,Massimo Vassalli,Delfina Costa,Aldo Pagano

doi:10.3389/fncel.2013.00203

Abstract

In the last decade the role of non coding (nc) RNAs in neurogenesis and in the onset of neurological diseases has been assessed by a multitude of studies. In this scenario, approximately 30 small RNA polymerase (pol) III–dependent ncRNAs were recently identified by computational tools and proposed as regulatory elements. The function of several of these transcripts was elucidated in vitro and in vivo confirming their involvement in cancer and in metabolic and neurodegenerative disorders. Emerging biophysical technologies together with the introduction of a physical perspective have been advantageous in regulatory RNA investigation providing original results on: (a) the differentiation of neuroblastoma (NB) cells towards a neuron-like phenotype triggered by Neuroblastoma Differentiation Marker 29 (NDM29) ncRNA; (b) the modulation of A-type K+ current in neurons induced by the small ncRNA 38A and (c) the synthesis driven by 17A ncRNA of a GABAB2 receptor isoform unable to trigger intracellular signaling. Moreover, the application of Single Cell Force Spectroscopy (SCFS) to these studies suggests a correlation between the malignancy stage of NB and the micro-adhesive properties of the cells, allowing to investigate the molecular basis of such a correlation.

Highlights

REGULATORY RNAs TRANSCRIBED BY POL III In the last few years polymerase III stepped in the limelight as a complex machinery that synthesizes a bulk of transcripts much higher than expected
Emerging biophysical technologies together with the introduction of a physical perspective have been advantageous in regulatory RNA investigation providing original results on: (a) the differentiation of neuroblastoma (NB) cells towards a neuron-like phenotype triggered by Neuroblastoma Differentiation Marker 29 (NDM29) ncRNA; (b) the modulation of A-type K+ current in neurons induced by the small ncRNA 38A and (c) the synthesis driven by 17A ncRNA of a GABAB2 receptor isoform unable to trigger intracellular signaling
Since 2007, a very active synthesis of non coding RNAs with regulatory features has been demonstrated (Pagano et al, 2007) and subsequently strengthened by further studies (Barski et al, 2010; Moqtaderi et al, 2010; Oler et al, 2010). These studies showed that pol III machinery is not to be considered as almost exclusively engaged in the synthesis of tRNAs and 5S ribosomal RNA, as this protein complex may transcribe in a cell type-/cell stage-specific manner a significant amount of small RNAs with regulatory features (Bruzzone et al, 2012; Garritano et al, 2012)

Summary

Introduction

REGULATORY RNAs TRANSCRIBED BY POL III In the last few years polymerase (pol) III stepped in the limelight as a complex machinery that synthesizes a bulk of transcripts much higher than expected. Emerging biophysical technologies together with the introduction of a physical perspective have been advantageous in regulatory RNA investigation providing original results on: (a) the differentiation of neuroblastoma (NB) cells towards a neuron-like phenotype triggered by Neuroblastoma Differentiation Marker 29 (NDM29) ncRNA; (b) the modulation of A-type K+ current in neurons induced by the small ncRNA 38A and (c) the synthesis driven by 17A ncRNA of a GABAB2 receptor isoform unable to trigger intracellular signaling.

Results

Conclusion