Co-reporter:Alessandro Bonetti, Piero Carninci
Current Opinion in Systems Biology 2017 Volume 3(Volume 3) pp:
Publication Date(Web):1 June 2017
DOI:10.1016/j.coisb.2017.04.016
•Alterations of lncRNAs expression can lead to a wide variety of diseases.•LncRNAs specificity can be exploited for the development of novel biomarkers.•ASOs targeting lncRNAs can ameliorate disorders phenotypes in animal models.•LncRNAs can modulate cell transcriptome and translatome.Long non-coding RNAs constitute the major transcriptional output of human genome. They are conveniently defined as RNA molecules longer than 200 nucleotides and not encoding proteins. Recent studies have highlighted the central role played by these transcripts in several physiological and pathological processes. Here we highlight how long non-coding RNAs have been used for diagnostic and therapeutic approaches and discuss how in the near future we can envision their application as pharmacological agents.
Co-reporter:Michiel de Hoon;Jay W. Shin
Mammalian Genome 2015 Volume 26( Issue 9-10) pp:391-402
Publication Date(Web):2015 October
DOI:10.1007/s00335-015-9593-8
Big leaps in science happen when scientists from different backgrounds interact. In the past 15 years, the FANTOM Consortium has brought together scientists from different fields to analyze and interpret genomic data produced with novel technologies, including mouse full-length cDNAs and, more recently, expression profiling at single-nucleotide resolution by cap-analysis gene expression. The FANTOM Consortium has provided the most comprehensive mouse cDNA collection for functional studies and extensive maps of the human and mouse transcriptome comprising promoters, enhancers, as well as the network of their regulatory interactions. More importantly, serendipitous observations of the FANTOM dataset led us to realize that the mammalian genome is pervasively transcribed, even from retrotransposon elements, which were previously considered junk DNA. The majority of products from the mammalian genome are long non-coding RNAs (lncRNAs), including sense-antisense, intergenic, and enhancer RNAs. While the biological function has been elucidated for some lncRNAs, more than 98 % of them remain without a known function. We argue that large-scale studies are urgently needed to address the functional role of lncRNAs.
Co-reporter:Kristoffer Vitting-Seerup;Carsten O. Daub;Erik Arner;Robin Andersson;Berit Lilje;Finn Drabløs;Andreas Lennartsson;Michelle Rönnerblad;Olga Hrydziuszko;Morana Vitezic;Tom C. Freeman;Ahmad M. N. Alhendi;Peter Arner;Richard Axton;J. Kenneth Baillie;Anthony Beckhouse;Beatrice Bodega;James Briggs;Frank Brombacher;Margaret Davis;Michael Detmar;Anna Ehrlund;Mitsuhiro Endoh;Afsaneh Eslami;Michela Fagiolini;Lynsey Fairbairn;Geoffrey J. Faulkner;Carmelo Ferrai;Malcolm E. Fisher;Lesley Forrester;Daniel Goldowitz;Reto Guler;Thomas Ha;Mitsuko Hara;Meenhard Herlyn;Tomokatsu Ikawa;Chieko Kai;Hiroshi Kawamoto;Levon M. Khachigian;S. Peter Klinken;Soichi Kojima;Haruhiko Koseki;Sarah Klein;Niklas Mejhert;Ken Miyaguchi;Yosuke Mizuno;Mitsuru Morimoto;Kelly J. Morris;Christine Mummery;Yutaka Nakachi;Soichi Ogishima;Mariko Okada-Hatakeyama;Yasushi Okazaki;Valerio Orlando;Dmitry Ovchinnikov;Robert Passier;Margaret Patrikakis;Ana Pombo;Xian-Yang Qin;Sugata Roy;Hiroki Sato;Suzana Savvi;Alka Saxena;Anita Schwegmann;Daisuke Sugiyama;Rolf Swoboda;Hiroshi Tanaka;Andru Tomoiu;Louise N. Winteringham;Ernst Wolvetang;Chiyo Yanagi-Mizuochi;Misako Yoneda;Susan Zabierowski;Peter Zhang;Imad Abugessaisa;Nicolas Bertin;Alexander D. Diehl;Shiro Fukuda;Masaaki Furuno;Jayson Harshbarger;Akira Hasegawa;Fumi Hori;Sachi Ishikawa-Kato;Yuri Ishizu;Masayoshi Itoh;Tsugumi Kawashima;Miki Kojima;Naoto Kondo;Marina Lizio;Terrence F. Meehan;Christopher J. Mungall;Mitsuyoshi Murata;Hiromi Nishiyori-Sueki;Serkan Sahin;Sayaka Nagao-Sato;Jessica Severin;Michiel J. L. de Hoon;Jun Kawai;Takeya Kasukawa;Timo Lassmann;Harukazu Suzuki;Hideya Kawaji;Kim M. Summers;Christine Wells;David A. Hume;Alistair R. R. Forrest;Albin Sandelin;Yoshihide Hayashizaki
Science 2015 Volume 347(Issue 6225) pp:1010-1014
Publication Date(Web):27 Feb 2015
DOI:10.1126/science.1259418
Uncaging promoter and enhancer dynamics
In order to understand cellular differentiation, it is important to understand the timing of the regulation of gene expression. Arner et al. used cap analysis of gene expression (CAGE) to analyze gene enhancer and promoter activities in a number of human and mouse cell types. The RNA of enhancers was transcribed first, followed by that of transcription factors, and finally by genes that are not transcription factors.
Science, this issue p. 1010
Co-reporter:Andreas Lennartsson;Erik Arner;Michela Fagiolini;Alka Saxena
Epigenetics & Chromatin 2015 Volume 8( Issue 1) pp:
Publication Date(Web):2015 December
DOI:10.1186/s13072-015-0043-3
The capacity for plasticity in the adult brain is limited by the anatomical traces laid down during early postnatal life. Removing certain molecular brakes, such as histone deacetylases (HDACs), has proven to be effective in recapitulating juvenile plasticity in the mature visual cortex (V1). We investigated the chromatin structure and transcriptional control by genome-wide sequencing of DNase I hypersensitive sites (DHSS) and cap analysis of gene expression (CAGE) libraries after HDAC inhibition by valproic acid (VPA) in adult V1.We found that VPA reliably reactivates the critical period plasticity and induces a dramatic change of chromatin organization in V1 yielding significantly greater accessibility distant from promoters, including at enhancer regions. VPA also induces nucleosome eviction specifically from retrotransposon (in particular SINE) elements. The transiently accessible SINE elements overlap with transcription factor-binding sites of the Fox family. Mapping of transcription start site activity using CAGE revealed transcription of epigenetic and neural plasticity-regulating genes following VPA treatment, which may help to re-program the genomic landscape and reactivate plasticity in the adult cortex.Treatment with HDAC inhibitors increases accessibility to enhancers and repetitive elements underlying brain-specific gene expression and reactivation of visual cortical plasticity.
Co-reporter:Boris Lenhard,
Albin Sandelin
&
Piero Carninci
Nature Reviews Genetics 2012 13(4) pp:233
Publication Date(Web):2012-03-06
DOI:10.1038/nrg3163
Promoters are crucial for gene regulation. They vary greatly in terms of associated regulatory elements, sequence motifs, the choice of transcription start sites and other features. Several technologies that harness next-generation sequencing have enabled recent advances in identifying promoters and their features, helping researchers who are investigating functional categories of promoters and their modes of regulation. Additional features of promoters that are being characterized include types of histone modifications, nucleosome positioning, RNA polymerase pausing and novel small RNAs. In this Review, we discuss recent findings relating to metazoan promoters and how these findings are leading to a revised picture of what a gene promoter is and how it works.
Co-reporter:Kaori Kashi, Lindsey Henderson, Alessandro Bonetti, Piero Carninci
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms (January 2016) Volume 1859(Issue 1) pp:
Publication Date(Web):January 2016
DOI:10.1016/j.bbagrm.2015.10.010
It is known that more than 70% of mammalian genomes are transcribed, yet the vast majority of transcripts do not code for proteins. Are these noncoding transcripts merely transcriptional noise, or do they serve a biological purpose? Recent developments in genomic analysis technologies, especially sequencing methods, have allowed researchers to create a large atlas of transcriptomes, study subcellular localization, and investigate potential interactions with proteins for a growing number of transcripts. Here, we review the current methodologies available for discovering and investigating functions of long noncoding RNAs (lncRNAs), which require a wide variety of applications to study their potential biological roles. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa.
