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

机译:Pol III转录的新型ncRNA并通过生物物理方法阐明其功能相关性

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摘要

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.
机译:在过去的十年中,已通过大量研究评估了非编码(nc)RNA在神经发生和神经系统疾病发作中的作用。在这种情况下,最近通过计算工具鉴定了约30种依赖小RNA聚合酶(pol)III的ncRNA,并被提议作为调控元件。在体外和体内阐明了其中一些转录物的功能,证实了它们参与了癌症以及代谢和神经退行性疾病。新兴的生物物理技术以及物理视角的引入在调节性RNA研究中具有优势,可提供以下方面的原始结果:(a)神经母细胞瘤(NB)细胞向神经母细胞瘤分化标记29(NDM29)ncRNA触发的神经元样表型的分化; (b)由小型ncRNA 38A诱导的神经元中A型K + 电流的调节,(c)由17A ncRNA驱动的无法触发细胞内信号转导的GABAB2受体亚型的合成。此外,单细胞力谱学(SCFS)在这些研究中的应用表明NB的恶性程度与细胞的微粘附特性之间存在相关性,从而可以研究这种相关性的分子基础。

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