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      The Role of lncRNAs in Gene Expression Regulation through mRNA Stabilization

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          Abstract

          mRNA stability influences gene expression and translation in almost all living organisms, and the levels of mRNA molecules in the cell are determined by a balance between production and decay. Maintaining an accurate balance is crucial for the correct function of a wide variety of biological processes and to maintain an appropriate cellular homeostasis. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of gene expression through different molecular mechanisms, including mRNA stabilization. In this review we provide an overview on the molecular mechanisms by which lncRNAs modulate mRNA stability and decay. We focus on how lncRNAs interact with RNA binding proteins and microRNAs to avoid mRNA degradation, and also on how lncRNAs modulate epitranscriptomic marks that directly impact on mRNA stability.

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          A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?

          Leonardo Salmena, Laura Poliseno, Yvonne Tay … (2011)
          Here, we present a unifying hypothesis about how messenger RNAs, transcribed pseudogenes, and long noncoding RNAs "talk" to each other using microRNA response elements (MREs) as letters of a new language. We propose that this "competing endogenous RNA" (ceRNA) activity forms a large-scale regulatory network across the transcriptome, greatly expanding the functional genetic information in the human genome and playing important roles in pathological conditions, such as cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
          Article 0 comments Cited 1966 times – based on 0 reviews     Review now
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            m6A-dependent regulation of messenger RNA stability

            Xiao Wang, Zhike Lu, Adrián Gómez-Brandón … (2013)
            N6 -methyladenosine (m6A) is the most prevalent internal (non-cap) modification present in the messenger RNA (mRNA) of all higher eukaryotes 1,2 . Although essential to cell viability and development 3–5 , the exact role of m6A modification remains to be determined. The recent discovery of two m6A demethylases in mammalian cells highlighted the importance of m6A in basic biological functions and disease 6–8 . Here we show that m6A is selectively recognized by the human YTH domain family 2 (YTHDF2) protein to regulate mRNA degradation. We identified over 3,000 cellular RNA targets of YTHDF2, most of which are mRNAs, but which also include non-coding RNAs, with a conserved core motif of G(m6A)C. We further establish the role of YTHDF2 in RNA metabolism, showing that binding of YTHDF2 results in the localization of bound mRNA from the translatable pool to mRNA decay sites, such as processing bodies 9 . The C-terminal domain of YTHDF2 selectively binds to m6A-containing mRNA whereas the N-terminal domain is responsible for the localization of the YTHDF2-mRNA complex to cellular RNA decay sites. Our results indicate that the dynamic m6A modification is recognized by selective-binding proteins to affect the translation status and lifetime of mRNA.
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              N(6)-methyladenosine Modulates Messenger RNA Translation Efficiency.

              Xiao Wang, Boxuan Simen Zhao, Ian A Roundtree … (2015)
              N(6)-methyladenosine (m(6)A) is the most abundant internal modification in mammalian mRNA. This modification is reversible and non-stoichiometric and adds another layer to the dynamic control of mRNA metabolism. The stability of m(6)A-modified mRNA is regulated by an m(6)A reader protein, human YTHDF2, which recognizes m(6)A and reduces the stability of target transcripts. Looking at additional functional roles for the modification, we find that another m(6)A reader protein, human YTHDF1, actively promotes protein synthesis by interacting with translation machinery. In a unified mechanism of m(6)A-based regulation in the cytoplasm, YTHDF2-mediated degradation controls the lifetime of target transcripts, whereas YTHDF1-mediated translation promotion increases translation efficiency, ensuring effective protein production from dynamic transcripts that are marked by m(6)A. Therefore, the m(6)A modification in mRNA endows gene expression with fast responses and controllable protein production through these mechanisms.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Noncoding RNA
                Journal ID (iso-abbrev): Noncoding RNA
                Journal ID (publisher-id): ncrna
                Title: Non-Coding RNA
                Publisher: MDPI
                ISSN (Electronic): 2311-553X
                Publication date (Electronic): 05 January 2021
                Publication date Collection: March 2021
                Volume: 7
                Issue: 1
                Electronic Location Identifier: 3
                Affiliations
                [1 ]Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country, 48940 Leioa, Spain; maialen.sebastian@ 123456ehu.eus (M.S.-d.); ane.olazagoitia@ 123456ehu.eus (A.O.-G.); ainara.castellanos@ 123456ehu.eus (A.C.-R.)
                [2 ]Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain; itziar.gonzalezm@ 123456ehu.eus
                [3 ]Department of Biochemistry and Molecular Biology, University of the Basque Country, 48940 Leioa, Spain
                [4 ]Ikerbasque, Basque Foundation for Science, 48009 Bilbao, Spain
                [5 ]CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain
                Author notes
                [* ]Correspondence: izortze.santin@ 123456ehu.eus ; Tel.: +34-94-601-32-09
                Author information
                https://orcid.org/0000-0003-2953-6573
                https://orcid.org/0000-0002-6504-4931
                https://orcid.org/0000-0003-3192-9544
                https://orcid.org/0000-0003-1651-6776
                Article
                Publisher ID: ncrna-07-00003
                DOI: 10.3390/ncrna7010003
                PMC ID: 7839045
                PubMed ID: 33466464
                SO-VID: ca0419d9-b17e-4f18-9527-31eecaaf23f0
                Copyright © © 2021 by the authors.
                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 ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 09 December 2020
                Date accepted : 30 December 2020
                Categories
                Subject: Review

                Keywords: long non-coding rna,mrna stability,rna binding protein,microrna,gene expression
                Data availability:
                Keywords: long non-coding rna, mrna stability, rna binding protein, microrna, gene expression

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