Brock Malcolm, Mei Yuping
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, 1650 Orleans Street, Baltimore, MD 21287, USA.
Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, 650 W Baltimore St, Baltimore, MD 21201, USA.
Cancer Lett. 2017 Sep 10;403:138-143. doi: 10.1016/j.canlet.2017.06.013. Epub 2017 Jun 19.
PIWI-interacting RNA Likes (piR-Ls) were recently reported to regulate functions of their target phospho-Proteins (p-Proteins) in somatic lung cells. However, the mechanism underlying this functionality remains unclear. piR-Ls interact with their targets through direct binding but do not follow base-pairing rules, known to have important roles at levels of transcription, RNA processing and translation for small non-coding RNA (sncRNA). These observations imply a fundamentally different type of sncRNA with behavior that causes a molecular response in their target p-Proteins. Furthermore, the interaction of piR-Ls with their targets regulates the functional efficacy of target p-Proteins. In addition, except for writers (kinase) and erasers (phosphatase), the functional efficacy of p-Proteins on their readers still remains unknown. It is reasonable to consider the existence of protein functional effector sncRNAs (pfeRNAs), which were identified by deep sequencing the immunoprecipitation products of antibodies targeting phosphorylated residues in proteins, as well as by functional analysis. pfeRNAs harbor unique features in size distribution, 3' terminal modification, shared core sequences, and functional manner, and could be new players in lung physiological and pathological conditions.
最近有报道称，PIWI相互作用RNA样分子（piR-Ls）可调节其靶标磷酸化蛋白（p-蛋白）在肺体细胞中的功能。然而，这种功能背后的机制仍不清楚。piR-Ls通过直接结合与其靶标相互作用，但不遵循碱基配对规则，而碱基配对规则在小非编码RNA（sncRNA）的转录、RNA加工和翻译水平上具有重要作用。这些观察结果表明，piR-Ls是一种本质上不同类型的sncRNA，其行为会在其靶标p-蛋白中引发分子反应。此外，piR-Ls与其靶标的相互作用调节了靶标p-蛋白的功能效力。此外，除了“书写者”（激酶）和“擦除者”（磷酸酶）外，p-蛋白对其“阅读者”的功能效力仍然未知。通过对靶向蛋白质中磷酸化残基的抗体免疫沉淀产物进行深度测序以及功能分析，鉴定出了蛋白质功能效应sncRNA（pfeRNA），因此有理由认为其存在。pfeRNA在大小分布、3'末端修饰、共享核心序列和功能方式方面具有独特特征，可能是肺部生理和病理状况中的新参与者。
