Abstract
Non-coding RNAs are pivotal for many cellular functions, such as splicing, gene regulation, chromosome structure, and hormone-like activity. Here, we will report about the biology and the general molecular mechanisms associated with long non-coding RNAs (lncRNAs), a class of >200 nucleotides-long ribonucleic acid sequences, and their role in chronic non-transmissible diseases. In particular, we will summarize knowledge about some of the best-characterized lncRNAs, such as H19 and MALAT1, and how they regulate carbohydrate and lipid metabolism as well as protein synthesis and degradation. Evidence is discussed about how lncRNAs expression might affect cellular and organismal metabolism and whether their modulation could provide ground for the development of innovative treatments.
Highlights
Non-coding RNAs are a class of ribonucleic acid sequences which do not carry any information for protein translation, at least not for long peptides, but are demonstrably involved in gene and protein regulation (Monticelli et al, 2005), RNA splicing (Kishore and Stamm, 2006), chromosome structure (Park et al, 2002) or, traveling through circulating blood, they play some hormone-like activities (Knoll et al, 2015)
Regarding long non-coding RNAs (lncRNAs), they include: imprinted lncRNAs, which control expression of imprinted genes (Sleutels et al, 2002); disease-associated lncRNAs which are abundant in pathophysiological conditions (Matouk et al, 2007; Yoshimizu et al, 2008); pathogen-induced lncRNAs which are produced and modulated by exogenous microorganisms (Zhou et al, 2016); bifunctional RNAs that can have more than one role and can be translated into proteins (Hashimoto et al, 2009); miRNA sponges that interfere with the inhibiting activity of miRNAs (Chen L. et al, 2018; Zhao et al, 2018)
pyruvate kinase isoform M2 (PKM2) seems involved in glucose metabolism, but it exists into the nucleus where acts as a kinase for some transcription factors, regulating the expression of proteins involved in hypoxia resistance, proliferation, glucose uptake, and mitosis progression (Gao et al, 2012). These findings suggest that PKM2 level could be modulated through H19 lncRNA which modulation might represent a potential new anticancer strategy
Summary
Non-coding RNAs (ncRNAs) are a class of ribonucleic acid sequences which do not carry any information for protein translation, at least not for long peptides, but are demonstrably involved in gene and protein regulation (Monticelli et al, 2005), RNA splicing (Kishore and Stamm, 2006), chromosome structure (Park et al, 2002) or, traveling through circulating blood, they play some hormone-like activities (Knoll et al, 2015). A specific lncRNAs signature, composed of six lncRNAs: uc010yfd., RNA147299| p0403_imsncRNA819, ENST00000444488.1, ASO3973, ENST00000602558.1, and ENST00000561165.1, has been recently identified in myocardial infarction (MI) and proposed as a sensitive biomarker of coronary disease (Li L. et al, 2018) In this pathophysiological condition, the cancer-associated lncRNA MALAT1 has been proposed to be of potential relevance, being highly expressed in the peripheral blood of infarcted mice (Hu et al, 2018) as a possible consequence of endogenous activation of the hypoxia pathway (Choudhry and Mole, 2016). High levels of the cardiachypertrophy-related factor (CHRF) lncRNA have been found associated with this pathophysiological condition This lncRNA sequesters miR-489, known to inhibit the mRNA encoding for the myeloid differentiation primary response gene product 88 (Myd88), increasing cardiomyocyte volume (Wang et al, 2014).
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