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      Non-Coding RNAs and their Integrated Networks

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          Abstract

          Eukaryotic genomes are pervasively transcribed. Besides protein-coding RNAs, there are different types of non-coding RNAs that modulate complex molecular and cellular processes. RNA sequencing technologies and bioinformatics methods greatly promoted the study of ncRNAs, which revealed ncRNAs’ essential roles in diverse aspects of biological functions. As important key players in gene regulatory networks, ncRNAs work with other biomolecules, including coding and non-coding RNAs, DNAs and proteins. In this review, we discuss the distinct types of ncRNAs, including housekeeping ncRNAs and regulatory ncRNAs, their versatile functions and interactions, transcription, translation, and modification. Moreover, we summarize the integrated networks of ncRNA interactions, providing a comprehensive landscape of ncRNAs regulatory roles.

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

            Laura Poliseno, Leonardo Salmena, JiangWen Zhang … (2010)
            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.
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              Ago HITS-CLIP decodes miRNA-mRNA interaction maps

              Sung Wook Chi, Julie B. Zang, Aldo Mele … (2009)
              Summary MicroRNAs (miRNAs) play critical roles in the regulation of gene expression. However, since miRNA activity requires base pairing with only 6-8 nucleotides of mRNA, predicting target mRNAs is a major challenge. Recently, high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) has identified functional protein-RNA interaction sites. Here we use HITS-CLIP to covalently crosslink native Argonaute (Ago) protein-RNA complexes in mouse brain. This produced two simultaneous datasets—Ago-miRNA and Ago-mRNA binding sites—that were combined with bioinformatic analysis to identify miRNA-target mRNA interaction sites. We validated genome-wide interaction maps for miR-124, and generated additional maps for the 20 most abundant miRNAs present in P13 mouse brain. Ago HITS-CLIP provides a general platform for exploring the specificity and range of miRNA action in vivo, and identifies precise sequences for targeting clinically relevant miRNA-mRNA interactions.
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                Author and article information

                Contributors
                Ming Chen
                Journal
                Journal ID (nlm-ta): J Integr Bioinform
                Journal ID (iso-abbrev): J Integr Bioinform
                Journal ID (publisher-id): jib
                Journal ID (doi): jib
                Journal ID (pmc): jib
                Title: Journal of Integrative Bioinformatics
                Publisher: De Gruyter
                ISSN (Electronic): 1613-4516
                Publication date (Electronic): 13 July 2019
                Publication date Collection: September 2019
                Volume: 16
                Issue: 3
                Electronic Location Identifier: 20190027
                Affiliations
                deptDepartment of Bioinformatics, State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences , Zhejiang University , Hangzhou 310058, China
                James D. Watson Institute of Genome Sciences, Zhejiang University , Hangzhou 310058, China
                Article
                Publisher ID: jib-2019-0027
                DOI: 10.1515/jib-2019-0027
                PMC ID: 6798851
                PubMed ID: 31301674
                SO-VID: 2dae5dc2-d713-486c-bcb1-6d75d1436738
                Copyright © © 2019, Peijing Zhang et al., published by Walter de Gruyter GmbH, Berlin/Boston
                License:

                This work is licensed under the Creative Commons Attribution 4.0 Public License.

                History
                Date received : 07 April 2019
                Date revision received : 02 May 2019
                Date accepted : 21 May 2019
                Page count
                Figures: 3, Tables: 1, References: 113, Pages: 12
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 31771477 and 31571366
                This work has been supported by the National Key Research and Development Program of China (Grant Nos. 2018YFC0310602 and 2016YFA0501704), National Natural Science Foundation of China (Funder Id: Funder Id: http://dx.doi.org/10.13039/501100001809, Grant Nos. 31771477 and 31571366), the Fundamental Research Funds for the Central Universities, Jiangsu Collaborative Innovation Center for Modern Crop Production and 2018 Zhejiang University Academic Award for Outstanding Doctoral Candidates.
                Categories
                Subject: Review Article

                Keywords: non-coding rna,integrated network,regulatory ncrna,ncrna interaction,cerna network
                Data availability:
                Keywords: non-coding rna, integrated network, regulatory ncrna, ncrna interaction, cerna network

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