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Long Noncoding RNAs: Genomics, Functions, Methodologies, Modes of Actions Wei Guifeng, guifengwei@ Institute of Biophysics, Chinese Academy of Sciences RNA Biology 1941 One Gene, One Enzyme 1953 DNA, double helix 1958 Crick, Central Dogma 1961 mRNA discovery Jacob Monod Lac Model 1966 hnRNA 1977 Intron discovery 1989 RNase P 1990 H19 lncRNA 1991 XIST 1993 lin-4 miRNA 1998 RNAi 1999 TSIX Small RNAs in PTGS Before 2000 2000 microRNAs * * After 2000 2001 Dicer in RNAi RNA in epigenetic regulation 2002 Many ncRNAs AIR in imprinting 2003 Drosha 2004 AGO2 2005 piRNAs Discovery of the CRISPR system of bacterial RNA-based defense 2007 HOTAIR 2009 Chromatin state and lincRNA 2010 Enhancer RNA 2012 ENCODE CRISPR/Cas9 RNA modification 2013 2014 Circular RNA RNA Biology * * The ENCODE Project Consortium. Nature 2012 ENCODE Project Yue Feng et al. Nature 2014 Long Noncoding RNAs ENCODE Project Extensive transcription / Genomics Igor Ulitsky et al. Cell 2013 Long Noncoding RNAs Igor Ulitsky et al. Cell 2013 Long Noncoding RNAs Long Noncoding RNAs Genomics Other forms of lncRNAs: sno-lncRNA, Circular RNA Long Noncoding RNAs Fatica et al. NAT. REV. GENETICS 2014 In Cis- or Trans Long Noncoding RNAs Fatica et al. NAT. REV. GENETICS 2014 In Cis- or Trans Long Noncoding RNAs Low abundance Tissue-specificity Moran Cabili et al. Genes Dev. 2011 Stem cell self-renewal and differentiation; Development and Lineage commitment; Immunology; Neurogenetics; Cancer progression (Tumor Suppressor or Oncogene); …… Long Noncoding RNAs Histone modification (HOTAIR), DNA methylation, high-order chromatin structure (Firre), transcription factor binding activity (RMST with SOX2), decoy model (PANDA), …… Long Noncoding RNAs HOTAIR affects expression of the HOXD gene family; XIST is crucial for the X chromosome inactivation; lincRNA-ROR affects reprogramming efficiency; Air is crucial for imprinting control at Igf2r locus; NRON affects NFAT transcription factor activity; Tug1 affects reti
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