1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Non-Coding RNA in Pancreas and β-Cell Development

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          In this review, we provide an overview of the current knowledge on the role of different classes of non-coding RNAs for islet and β-cell development, maturation and function. MicroRNAs (miRNAs), a prominent class of small RNAs, have been investigated for more than two decades and patterns of the roles of different miRNAs in pancreatic fetal development, islet and β-cell maturation and function are now emerging. Specific miRNAs are dynamically regulated throughout the period of pancreas development, during islet and β-cell differentiation as well as in the perinatal period, where a burst of β-cell replication takes place. The role of long non-coding RNAs (lncRNA) in islet and β-cells is less investigated than for miRNAs, but knowledge is increasing rapidly. The advent of ultra-deep RNA sequencing has enabled the identification of highly islet- or β-cell-selective lncRNA transcripts expressed at low levels. Their roles in islet cells are currently only characterized for a few of these lncRNAs, and these are often associated with β-cell super-enhancers and regulate neighboring gene activity. Moreover, ncRNAs present in imprinted regions are involved in pancreas development and β-cell function. Altogether, these observations support significant and important actions of ncRNAs in β-cell development and function.

          Related collections

          Most cited references138

          • Record: found
          • Abstract: found
          • Article: not found

          Origins and Mechanisms of miRNAs and siRNAs.

          Over the last decade, approximately 20-30 nucleotide RNA molecules have emerged as critical regulators in the expression and function of eukaryotic genomes. Two primary categories of these small RNAs--short interfering RNAs (siRNAs) and microRNAs (miRNAs)--act in both somatic and germline lineages in a broad range of eukaryotic species to regulate endogenous genes and to defend the genome from invasive nucleic acids. Recent advances have revealed unexpected diversity in their biogenesis pathways and the regulatory mechanisms that they access. Our understanding of siRNA- and miRNA-based regulation has direct implications for fundamental biology as well as disease etiology and treatment.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            A coding-independent function of gene and pseudogene mRNAs regulates tumour biology

            The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs possess a biological role in cancer cells that relies upon their ability to compete for microRNA binding and is independent of their protein-coding function. As a paradigm for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene (PTENP1) and the critical consequences of this interaction. We find that PTENP1 is biologically active as determined by its ability to regulate cellular levels of PTEN, and that it can exert a growth-suppressive role. We also show that PTENP1 locus is selectively lost in human cancer. We extend our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. Further, we demonstrate that the transcripts of protein coding genes such as PTEN are also biologically active. Together, these findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Nuclear export of microRNA precursors.

              MicroRNAs (miRNAs), which function as regulators of gene expression in eukaryotes, are processed from larger transcripts by sequential action of nuclear and cytoplasmic ribonuclease III-like endonucleases. We show that Exportin-5 (Exp5) mediates efficient nuclear export of short miRNA precursors (pre-miRNAs) and that its depletion by RNA interference results in reduced miRNA levels. Exp5 binds correctly processed pre-miRNAs directly and specifically, in a Ran guanosine triphosphate-dependent manner, but interacts only weakly with extended pre-miRNAs that yield incorrect miRNAs when processed by Dicer in vitro. Thus, Exp5 is key to miRNA biogenesis and may help coordinate nuclear and cytoplasmic processing steps.
                Bookmark

                Author and article information

                Journal
                Noncoding RNA
                Noncoding RNA
                ncrna
                Non-Coding RNA
                MDPI
                2311-553X
                13 December 2018
                December 2018
                : 4
                : 4
                : 41
                Affiliations
                [1 ]NHMRC Clinical Trials Center, University of Sydney, Camperdown, Sydney, NSW 2050, Australia; wilson.wong@ 123456ctc.usyd.edu.au (W.K.M.W.); mugdha.joglekar@ 123456ctc.usyd.edu.au (M.V.J.); anand.hardikar@ 123456ctc.usyd.edu.au (A.A.H.)
                [2 ]Department of Science and Environment, Roskilde University, DK-4000 Roskilde, Denmark; elaine@ 123456ruc.dk
                Author notes
                [* ]Correspondence: ltd@ 123456ruc.dk ; Tel.: +45-4674-2713
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-3598-2775
                Article
                ncrna-04-00041
                10.3390/ncrna4040041
                6315983
                30551650
                cd0d6d81-529e-42e9-9862-e83376bc5cf3
                © 2018 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/).

                History
                : 21 November 2018
                : 11 December 2018
                Categories
                Review

                non-coding rnas,long non-coding rnas,long intergenic non-coding rnas,microrna,small nucleolar rnas,piwi associated rnas,circular rnas,β-cell,α-cell,islets of langerhans,pancreas,fetal development

                Comments

                Comment on this article