Non-Coding RNAs: Novel Players in Insulin Resistance and Related Diseases

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Abstract

The rising prevalence of metabolic diseases related to insulin resistance (IR) have stressed the urgent need of accurate and applicable tools for early diagnosis and treatment. In the last decade, non-coding RNAs (ncRNAs) have gained growing interest because of their potential role in IR modulation. NcRNAs are variable-length transcripts which are not translated into proteins but are involved in gene expression regulation. Thanks to their stability and easy detection in biological fluids, ncRNAs have been investigated as promising diagnostic and therapeutic markers in metabolic diseases, such as type 2 diabetes mellitus (T2D), obesity and non-alcoholic fatty liver disease (NAFLD). Here we review the emerging role of ncRNAs in the development of IR and related diseases such as obesity, T2D and NAFLD, and summarize current evidence concerning their potential clinical application.

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Circular RNAs are a large class of animal RNAs with regulatory potency.

Sebastian Memczak, Marvin Jens, Antigoni Elefsinioti … (2013)

Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.

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The biogenesis, biology and characterization of circular RNAs

Lasse S. Kristensen, Maria Andersen, Lotte V. W. Stagsted … (2019)

Circular RNAs (circRNAs) are covalently closed, endogenous biomolecules in eukaryotes with tissue-specific and cell-specific expression patterns, whose biogenesis is regulated by specific cis-acting elements and trans-acting factors. Some circRNAs are abundant and evolutionarily conserved, and many circRNAs exert important biological functions by acting as microRNA or protein inhibitors ('sponges'), by regulating protein function or by being translated themselves. Furthermore, circRNAs have been implicated in diseases such as diabetes mellitus, neurological disorders, cardiovascular diseases and cancer. Although the circular nature of these transcripts makes their detection, quantification and functional characterization challenging, recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of state-of-the-art approaches for their identification, and novel approaches to functional characterization are emerging.

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Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation

Jacob O'Brien, Heyam Hayder, Yara Zayed … (2018)

MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in regulating gene expression. The majority of miRNAs are transcribed from DNA sequences into primary miRNAs and processed into precursor miRNAs, and finally mature miRNAs. In most cases, miRNAs interact with the 3′ untranslated region (3′ UTR) of target mRNAs to induce mRNA degradation and translational repression. However, interaction of miRNAs with other regions, including the 5′ UTR, coding sequence, and gene promoters, have also been reported. Under certain conditions, miRNAs can also activate translation or regulate transcription. The interaction of miRNAs with their target genes is dynamic and dependent on many factors, such as subcellular location of miRNAs, the abundancy of miRNAs and target mRNAs, and the affinity of miRNA-mRNA interactions. miRNAs can be secreted into extracellular fluids and transported to target cells via vesicles, such as exosomes, or by binding to proteins, including Argonautes. Extracellular miRNAs function as chemical messengers to mediate cell-cell communication. In this review, we provide an update on canonical and non-canonical miRNA biogenesis pathways and various mechanisms underlying miRNA-mediated gene regulations. We also summarize the current knowledge of the dynamics of miRNA action and of the secretion, transfer, and uptake of extracellular miRNAs.

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Author and article information

Contributors

Melania Manco: Role: Academic Editor

Amalia Gastaldelli: Role: Academic Editor

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 19 July 2021

Publication date Collection: July 2021

Volume: 22

Issue: 14

Electronic Location Identifier: 7716

Affiliations

[1 ]Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy; catefo@ 123456libero.it (C.F.); launigi@ 123456gmail.com (L.N.); giusy.grieco.90@ 123456gmail.com (G.E.G.); dfignani@ 123456gmail.com (D.F.); noemibrusco91@ 123456gmail.com (N.B.); giadalicata.92@ 123456gmail.com (G.L.); sebastianiguido@ 123456gmail.com (G.S.)

[2 ]Fondazione Umberto Di Mario, c/o Toscana Life Sciences, 53100 Siena, Italy

[3 ]Section of Medical Pathophysiology, Food Science and Endocrinology, Department of Experimental Medicine, Sapienza University, 00185 Rome, Italy; carla.maccora@ 123456gmail.com

[4 ]Tuscany Centre for Precision Medicine (CReMeP), 53100 Siena, Italy

Author notes

[* ]Correspondence: francesco.dotta@ 123456unisi.it ; Tel.: +39-0577-231283

[†]

Shared first authorship.

Author information

Giuseppina Emanuela Grieco https://orcid.org/0000-0001-7325-6128

Giada Licata https://orcid.org/0000-0001-6995-8581

Article

Publisher ID: ijms-22-07716

DOI: 10.3390/ijms22147716

PMC ID: 8306942

PubMed ID: 34299336

SO-VID: 5468dd9f-5aa2-4687-9f68-6145cc382952

License:

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 ( https://creativecommons.org/licenses/by/4.0/).

Non-Coding RNAs: Novel Players in Insulin Resistance and Related Diseases

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Karger: Nutrition and Dietetics

Most cited references 217

Circular RNAs are a large class of animal RNAs with regulatory potency.

The biogenesis, biology and characterization of circular RNAs

Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation

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