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      Non-coding RNAs as drug targets

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      Journal: Nature Reviews Drug Discovery
      Publisher: Springer Nature

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          Abstract

          Non-coding RNAs (ncRNAs) may affect normal gene expression and disease progression, thereby representing potential drug targets. Here, Matsui and Corey assess the potential and challenges in therapeutically exploiting ncRNA species — including microRNA, intronic RNA, repetitive RNA and long ncRNA — highlighting key lessons learned during the development of technologies targeting mRNA.

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          The transcriptional landscape of the mammalian genome.

          P Carninci, T Kasukawa, S. Katayama … (2005)
          This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
          Article 0 comments Cited 1256 times – based on 0 reviews     Review now
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            RNA maps reveal new RNA classes and a possible function for pervasive transcription.

            Philipp Kapranov, Jill Cheng, Sujit Dike … (2007)
            Significant fractions of eukaryotic genomes give rise to RNA, much of which is unannotated and has reduced protein-coding potential. The genomic origins and the associations of human nuclear and cytosolic polyadenylated RNAs longer than 200 nucleotides (nt) and whole-cell RNAs less than 200 nt were investigated in this genome-wide study. Subcellular addresses for nucleotides present in detected RNAs were assigned, and their potential processing into short RNAs was investigated. Taken together, these observations suggest a novel role for some unannotated RNAs as primary transcripts for the production of short RNAs. Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes. These data support a highly interleaved organization of the human transcriptome.
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              Landscape of transcription in human cells

              Sarah Djebali, Carrie A. Davis, Angelika Merkel … (2012)
              Summary Eukaryotic cells make many types of primary and processed RNAs that are found either in specific sub-cellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic sub-cellular localizations are also poorly understood. Since RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell’s regulatory capabilities are focused on its synthesis, processing, transport, modifications and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations taken together prompt to a redefinition of the concept of a gene.
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                Author and article information

                Journal
                Title: Nature Reviews Drug Discovery
                Abbreviated Title: Nat Rev Drug Discov
                Publisher: Springer Nature
                ISSN (Print): 1474-1776
                ISSN (Electronic): 1474-1784
                Publication date Created: July 22 2016
                Publication date (Print): July 22 2016
                Volume:
                Issue:
                Article
                DOI: 10.1038/nrd.2016.117
                PMC ID: 5831170
                PubMed ID: 27444227
                SO-VID: 873577ff-d126-499a-b80a-556209124fba
                Copyright statement: © 2016
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                Self URI (article page): http://www.nature.com/doifinder/10.1038/nrd.2016.117

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