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Deciphering miRNAs’ Action through miRNA Editing

MicroRNAs (miRNAs) are small non-coding RNAs with the capability of modulating gene expression at the post-transcriptional level either by inhibiting messenger RNA (mRNA) translation or by promoting mRNA degradation. The outcome of a myriad of physiological processes and pathologies, including cance...

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Autores principales: Correia de Sousa, Marta, Gjorgjieva, Monika, Dolicka, Dobrochna, Sobolewski, Cyril, Foti, Michelangelo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941098/
https://www.ncbi.nlm.nih.gov/pubmed/31835747
http://dx.doi.org/10.3390/ijms20246249
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author Correia de Sousa, Marta
Gjorgjieva, Monika
Dolicka, Dobrochna
Sobolewski, Cyril
Foti, Michelangelo
author_facet Correia de Sousa, Marta
Gjorgjieva, Monika
Dolicka, Dobrochna
Sobolewski, Cyril
Foti, Michelangelo
author_sort Correia de Sousa, Marta
collection PubMed
description MicroRNAs (miRNAs) are small non-coding RNAs with the capability of modulating gene expression at the post-transcriptional level either by inhibiting messenger RNA (mRNA) translation or by promoting mRNA degradation. The outcome of a myriad of physiological processes and pathologies, including cancer, cardiovascular and metabolic diseases, relies highly on miRNAs. However, deciphering the precise roles of specific miRNAs in these pathophysiological contexts is challenging due to the high levels of complexity of their actions. Indeed, regulation of mRNA expression by miRNAs is frequently cell/organ specific; highly dependent on the stress and metabolic status of the organism; and often poorly correlated with miRNA expression levels. Such biological features of miRNAs suggest that various regulatory mechanisms control not only their expression, but also their activity and/or bioavailability. Several mechanisms have been described to modulate miRNA action, including genetic polymorphisms, methylation of miRNA promoters, asymmetric miRNA strand selection, interactions with RNA-binding proteins (RBPs) or other coding/non-coding RNAs. Moreover, nucleotide modifications (A-to-I or C-to-U) within the miRNA sequences at different stages of their maturation are also critical for their functionality. This regulatory mechanism called “RNA editing” involves specific enzymes of the adenosine/cytidine deaminase family, which trigger single nucleotide changes in primary miRNAs. These nucleotide modifications greatly influence a miRNA’s stability, maturation and activity by changing its specificity towards target mRNAs. Understanding how editing events impact miRNA’s ability to regulate stress responses in cells and organs, or the development of specific pathologies, e.g., metabolic diseases or cancer, should not only deepen our knowledge of molecular mechanisms underlying complex diseases, but can also facilitate the design of new therapeutic approaches based on miRNA targeting. Herein, we will discuss the current knowledge on miRNA editing and how this mechanism regulates miRNA biogenesis and activity.
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spelling pubmed-69410982020-01-09 Deciphering miRNAs’ Action through miRNA Editing Correia de Sousa, Marta Gjorgjieva, Monika Dolicka, Dobrochna Sobolewski, Cyril Foti, Michelangelo Int J Mol Sci Review MicroRNAs (miRNAs) are small non-coding RNAs with the capability of modulating gene expression at the post-transcriptional level either by inhibiting messenger RNA (mRNA) translation or by promoting mRNA degradation. The outcome of a myriad of physiological processes and pathologies, including cancer, cardiovascular and metabolic diseases, relies highly on miRNAs. However, deciphering the precise roles of specific miRNAs in these pathophysiological contexts is challenging due to the high levels of complexity of their actions. Indeed, regulation of mRNA expression by miRNAs is frequently cell/organ specific; highly dependent on the stress and metabolic status of the organism; and often poorly correlated with miRNA expression levels. Such biological features of miRNAs suggest that various regulatory mechanisms control not only their expression, but also their activity and/or bioavailability. Several mechanisms have been described to modulate miRNA action, including genetic polymorphisms, methylation of miRNA promoters, asymmetric miRNA strand selection, interactions with RNA-binding proteins (RBPs) or other coding/non-coding RNAs. Moreover, nucleotide modifications (A-to-I or C-to-U) within the miRNA sequences at different stages of their maturation are also critical for their functionality. This regulatory mechanism called “RNA editing” involves specific enzymes of the adenosine/cytidine deaminase family, which trigger single nucleotide changes in primary miRNAs. These nucleotide modifications greatly influence a miRNA’s stability, maturation and activity by changing its specificity towards target mRNAs. Understanding how editing events impact miRNA’s ability to regulate stress responses in cells and organs, or the development of specific pathologies, e.g., metabolic diseases or cancer, should not only deepen our knowledge of molecular mechanisms underlying complex diseases, but can also facilitate the design of new therapeutic approaches based on miRNA targeting. Herein, we will discuss the current knowledge on miRNA editing and how this mechanism regulates miRNA biogenesis and activity. MDPI 2019-12-11 /pmc/articles/PMC6941098/ /pubmed/31835747 http://dx.doi.org/10.3390/ijms20246249 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Correia de Sousa, Marta
Gjorgjieva, Monika
Dolicka, Dobrochna
Sobolewski, Cyril
Foti, Michelangelo
Deciphering miRNAs’ Action through miRNA Editing
title Deciphering miRNAs’ Action through miRNA Editing
title_full Deciphering miRNAs’ Action through miRNA Editing
title_fullStr Deciphering miRNAs’ Action through miRNA Editing
title_full_unstemmed Deciphering miRNAs’ Action through miRNA Editing
title_short Deciphering miRNAs’ Action through miRNA Editing
title_sort deciphering mirnas’ action through mirna editing
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941098/
https://www.ncbi.nlm.nih.gov/pubmed/31835747
http://dx.doi.org/10.3390/ijms20246249
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