The Non-Canonical Aspects of MicroRNAs: Many Roads to Gene Regulation

MicroRNAs (miRNAs) are critical regulators of gene expression. As miRNAs are frequently deregulated in many human diseases, including cancer and immunological disorders, it is important to understand their biological functions. Typically, miRNA-encoding genes are transcribed by RNA Polymerase II and...

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Main Authors: Christiaan J. Stavast, Stefan J. Erkeland
Format: Article
Language:English
Published: MDPI AG 2019-11-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/8/11/1465
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author Christiaan J. Stavast
Stefan J. Erkeland
author_facet Christiaan J. Stavast
Stefan J. Erkeland
author_sort Christiaan J. Stavast
collection DOAJ
description MicroRNAs (miRNAs) are critical regulators of gene expression. As miRNAs are frequently deregulated in many human diseases, including cancer and immunological disorders, it is important to understand their biological functions. Typically, miRNA-encoding genes are transcribed by RNA Polymerase II and generate primary transcripts that are processed by RNase III-endonucleases DROSHA and DICER into small RNAs of approximately 21 nucleotides. All miRNAs are loaded into Argonaute proteins in the RNA-induced silencing complex (RISC) and act as post-transcriptional regulators by binding to the 3′- untranslated region (UTR) of mRNAs. This seed-dependent miRNA binding inhibits the translation and/or promotes the degradation of mRNA targets. Surprisingly, recent data presents evidence for a target-mediated decay mechanism that controls the level of specific miRNAs. In addition, several non-canonical miRNA-containing genes have been recently described and unexpected functions of miRNAs have been identified. For instance, several miRNAs are located in the nucleus, where they are involved in the transcriptional activation or silencing of target genes. These epigenetic modifiers are recruited by RISC and guided by miRNAs to specific loci in the genome. Here, we will review non-canonical aspects of miRNA biology, including novel regulators of miRNA expression and functions of miRNAs in the nucleus.
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spelling doaj.art-af2196bd956c4634a3a51f48865b053c2023-09-02T15:21:17ZengMDPI AGCells2073-44092019-11-01811146510.3390/cells8111465cells8111465The Non-Canonical Aspects of MicroRNAs: Many Roads to Gene RegulationChristiaan J. Stavast0Stefan J. Erkeland1Department of Immunology, Erasmus University Medical Center, Dr. Molenwaterplein 40, 3015GD Rotterdam, The NetherlandsDepartment of Immunology, Erasmus University Medical Center, Dr. Molenwaterplein 40, 3015GD Rotterdam, The NetherlandsMicroRNAs (miRNAs) are critical regulators of gene expression. As miRNAs are frequently deregulated in many human diseases, including cancer and immunological disorders, it is important to understand their biological functions. Typically, miRNA-encoding genes are transcribed by RNA Polymerase II and generate primary transcripts that are processed by RNase III-endonucleases DROSHA and DICER into small RNAs of approximately 21 nucleotides. All miRNAs are loaded into Argonaute proteins in the RNA-induced silencing complex (RISC) and act as post-transcriptional regulators by binding to the 3′- untranslated region (UTR) of mRNAs. This seed-dependent miRNA binding inhibits the translation and/or promotes the degradation of mRNA targets. Surprisingly, recent data presents evidence for a target-mediated decay mechanism that controls the level of specific miRNAs. In addition, several non-canonical miRNA-containing genes have been recently described and unexpected functions of miRNAs have been identified. For instance, several miRNAs are located in the nucleus, where they are involved in the transcriptional activation or silencing of target genes. These epigenetic modifiers are recruited by RISC and guided by miRNAs to specific loci in the genome. Here, we will review non-canonical aspects of miRNA biology, including novel regulators of miRNA expression and functions of miRNAs in the nucleus.https://www.mdpi.com/2073-4409/8/11/1465micrornasbiogenesisnuclear localizationtranscriptional regulationnon-canonical
spellingShingle Christiaan J. Stavast
Stefan J. Erkeland
The Non-Canonical Aspects of MicroRNAs: Many Roads to Gene Regulation
Cells
micrornas
biogenesis
nuclear localization
transcriptional regulation
non-canonical
title The Non-Canonical Aspects of MicroRNAs: Many Roads to Gene Regulation
title_full The Non-Canonical Aspects of MicroRNAs: Many Roads to Gene Regulation
title_fullStr The Non-Canonical Aspects of MicroRNAs: Many Roads to Gene Regulation
title_full_unstemmed The Non-Canonical Aspects of MicroRNAs: Many Roads to Gene Regulation
title_short The Non-Canonical Aspects of MicroRNAs: Many Roads to Gene Regulation
title_sort non canonical aspects of micrornas many roads to gene regulation
topic micrornas
biogenesis
nuclear localization
transcriptional regulation
non-canonical
url https://www.mdpi.com/2073-4409/8/11/1465
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