Activating the Chromatin by Noncoding RNAs

Laham-Karam, Nihay; Laitinen, Pia; Turunen, Tiia A.; Ylä‐Herttuala, Seppo

doi:10.1089/ars.2017.7248

Cited by 20 publications

(11 citation statements)

References 169 publications

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“…For example, small RNA-mediated transcriptional gene activation (TGA) has been reported in some cases, whereby synthetic small RNAs or endogenous miRNAs targeted to gene promoters can induce increases in gene expression 6,7 . TGA involves an epigenetic mechanism, although a detailed understanding of this phenomenon has thus far remained elusive 8 .…”

Section: Introductionmentioning

confidence: 99%

Changes in nuclear and cytoplasmic microRNA distribution in response to hypoxic stress

Turunen

Roberts

Laitinen

et al. 2019

Sci Rep

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MicroRNAs (miRNAs) are small non-coding RNAs that have well-characterized roles in cytoplasmic gene regulation, where they act by binding to mRNA transcripts and inhibiting their translation (i.e. post-transcriptional gene silencing, PTGS). However, miRNAs have also been implicated in transcriptional gene regulation and alternative splicing, events that are restricted to the cell nucleus. Here we performed nuclear-cytoplasmic fractionation in a mouse endothelial cell line and characterized the localization of miRNAs in response to hypoxia using small RNA sequencing. A highly diverse population of abundant miRNA species was detected in the nucleus, of which the majority (56%) was found to be preferentially localized in one compartment or the other. Induction of hypoxia resulted in changes in miRNA levels in both nuclear and cytoplasmic compartments, with the majority of changes being restricted to one location and not the other. Notably, the classical hypoxamiR (miR-210-3p) was highly up-regulated in the nuclear compartment after hypoxic stimulus. These findings reveal a previously unappreciated level of molecular complexity in the physiological response occurring in ischemic tissue. Furthermore, widespread differential miRNA expression in the nucleus strongly suggests that these small RNAs are likely to perform extensive nuclear regulatory functions in the general case.

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Section: Introductionmentioning

confidence: 99%

Changes in nuclear and cytoplasmic microRNA distribution in response to hypoxic stress

Turunen

Roberts

Laitinen

et al. 2019

Sci Rep

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“…145 The ncRNAs play a crucial role in gene regulation processes and epigenetic changes. 146,147 The Long intergenic non-coding RNAs (lincRNAs) have been reported to play significant roles in a number of diseases, including coronary atherosclerosis, 148 immune disease, 149 and different type of malignancies. 150 Over the years, many experimental findings have demonstrated that lincRNAs have significant roles in the pathogenesis of cardiovascular disease.…”

Section: Non-coding Rnasmentioning

confidence: 99%

Elucidation of Epigenetic Landscape in Coronary Artery Disease: A Review on Basic Concept to Personalized Medicine

et al. 2021

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Despite extensive clinical research and management protocols applied in the field of coronary artery diseases (CAD), it still holds the number 1 position in mortality worldwide. This indicates that we need to work on precision medicine to discover the diagnostic, therapeutic, and prognostic targets to improve the outcome of CAD. In precision medicine, epigenetic changes play a vital role in disease onset and progression. Epigenetics is the study of heritable changes that do not affect the alterations of DNA sequence in the genome. It comprises various covalent modifications that occur in DNA or histone proteins affecting the spatial arrangement of the DNA and histones. These multiple modifications include DNA/histone methylation, acetylation, phosphorylation, and SUMOylation. Besides these covalent modifications, non-coding RNAs—viz. miRNA, lncRNA, and circRNA are also involved in epigenetics. Smoking, alcohol, diet, environmental pollutants, obesity, and lifestyle are some of the prime factors affecting epigenetic alterations. Novel molecular techniques such as next-generation sequencing, chromatin immunoprecipitation, and mass spectrometry have been developed to identify important cross points in the epigenetic web in relation to various diseases. The studies regarding exploration of epigenetics, have led researchers to identify multiple diagnostic markers and therapeutic targets that are being used in different disease diagnosis and management. Here in this review, we will discuss various ground-breaking contributions of past and recent studies in the epigenetic field in concert with coronary artery diseases. Future prospects of epigenetics and its implication in CAD personalized medicine will also be discussed in brief.

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“…RNA therapeutic avenues are likely to extend in the future, as we are not limited to RNAi mechanisms in the cytoplasm but dsRNAs can also act in the nucleus to cause transcriptional gene silencing (TGS) via modification of epigenetic marks (Castel and Martienssen, 2013;Martienssen and Moazed, 2015). In addition, siRNA targeting gene promoters can also cause transcriptional activation (Laham-Karam et al, 2018), these transcription regulating small RNA can expand the repertoire of the RNA therapeutics and are likely to reach the clinics in future.…”

Section: Rna Interference-based Inhibitorsmentioning

confidence: 99%

Transcription and Translation Inhibitors in Cancer Treatment

et al. 2020

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Transcription and translation are fundamental cellular processes that govern the protein production of cells. These processes are generally up regulated in cancer cells, to maintain the enhanced metabolism and proliferative state of these cells. As such cancerous cells can be susceptible to transcription and translation inhibitors. There are numerous druggable proteins involved in transcription and translation which make lucrative targets for cancer drug development. In addition to proteins, recent years have shown that the "undruggable" transcription factors and RNA molecules can also be targeted to hamper the transcription or translation in cancer. In this review, we summarize the properties and function of the transcription and translation inhibitors that have been tested and developed, focusing on the advances of the last 5 years. To complement this, we also discuss some of the recent advances in targeting oncogenes tightly controlling transcription including transcription factors and KRAS. In addition to natural and synthetic compounds, we review DNA and RNA based approaches to develop cancer drugs. Finally, we conclude with the outlook to the future of the development of transcription and translation inhibitors.

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Activating the Chromatin by Noncoding RNAs

Cited by 20 publications

References 169 publications

Changes in nuclear and cytoplasmic microRNA distribution in response to hypoxic stress

Changes in nuclear and cytoplasmic microRNA distribution in response to hypoxic stress

Elucidation of Epigenetic Landscape in Coronary Artery Disease: A Review on Basic Concept to Personalized Medicine

Transcription and Translation Inhibitors in Cancer Treatment

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