Regulation of transcription by long noncoding RNAs.

Over the past decade there has been a greater understanding of genomic complexity in eukaryotes ushered in by the immense technological advances in high-throughput sequencing of DNA and its corresponding RNA transcripts. This has resulted in the realization that beyond protein-coding genes, there are a large number of transcripts that do not encode for proteins and, therefore, may perform their function through RNA sequences and/or through secondary and tertiary structural determinants. This review is focused on the latest findings on a class of noncoding RNAs that are relatively large (>200 nucleotides), display nuclear localization, and use different strategies to regulate transcription. These are exciting times for discovering the biological scope and the mechanism of action for these RNA molecules, which have roles in dosage compensation, imprinting, enhancer function, and transcriptional regulation, with a great impact on development and disease.

[1]  Fred Winston,et al.  in Saccharomyces cerevisiae , 2005 .

[2]  J. Rinn,et al.  Modular regulatory principles of large non-coding RNAs , 2012, Nature.

[3]  Guennaelle Dieppois,et al.  Antisense RNA Stabilization Induces Transcriptional Gene Silencing via Histone Deacetylation in S. cerevisiae , 2007, Cell.

[4]  Rhiju Das,et al.  Quantitative dimethyl sulfate mapping for automated RNA secondary structure inference. , 2012, Biochemistry.

[5]  J. Komorowski,et al.  Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. , 2008, Molecular cell.

[6]  Toshiro K. Ohsumi,et al.  Genome-wide identification of polycomb-associated RNAs by RIP-seq. , 2010, Molecular cell.

[7]  Michael Morse,et al.  Multiple knockout mouse models reveal lincRNAs are required for life and brain development , 2013, eLife.

[8]  R. Maeda,et al.  abd-A Regulation by the iab-8 Noncoding RNA , 2012, PLoS genetics.

[9]  Paul Lasko,et al.  Drosophila Pgc protein inhibits P-TEFb recruitment to chromatin in primordial germ cells , 2008, Nature.

[10]  R. Plasterk,et al.  The genetics of RNA silencing. , 2002, Annual review of genetics.

[11]  J. Rinn,et al.  Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression , 2009, Proceedings of the National Academy of Sciences.

[12]  R Berezney,et al.  Identification of a nuclear protein matrix. , 1974, Biochemical and biophysical research communications.

[13]  Thomas R. Gingeras,et al.  Molecular biology: RNA discrimination , 2012, Nature.

[14]  T. Cech,et al.  Self-splicing RNA: Autoexcision and autocyclization of the ribosomal RNA intervening sequence of tetrahymena , 1982, Cell.

[15]  T. Jenuwein,et al.  Higher-order structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA component , 2002, Nature Genetics.

[16]  Gos Micklem,et al.  Supporting Online Material Materials and Methods Figs. S1 to S50 Tables S1 to S18 References Identification of Functional Elements and Regulatory Circuits by Drosophila Modencode , 2022 .

[17]  E. Lewis C. B. Bridges' repeat hypothesis and the nature of the gene. , 2003, Genetics.

[18]  Nicholas T. Ingolia,et al.  Ribosome Profiling Provides Evidence that Large Noncoding RNAs Do Not Encode Proteins , 2013, Cell.

[19]  D. Reinberg,et al.  Interactions with RNA direct the Polycomb group protein SCML2 to chromatin where it represses target genes , 2014, eLife.

[20]  Albert E. Almada,et al.  Divergent transcription of long noncoding RNA/mRNA gene pairs in embryonic stem cells , 2013, Proceedings of the National Academy of Sciences.

[21]  T. Derrien,et al.  Long Noncoding RNAs with Enhancer-like Function in Human Cells , 2010, Cell.

[22]  W. Bender,et al.  Noncoding RNAs of the Ultrabithorax Domain of the Drosophila Bithorax Complex , 2013, Genetics.

[23]  E. Mardis Next-generation sequencing platforms. , 2013, Annual review of analytical chemistry.

[24]  Jennifer E. Phillips-Cremins,et al.  Architectural Protein Subclasses Shape 3D Organization of Genomes during Lineage Commitment , 2013, Cell.

[25]  Pieter C. Dorrestein,et al.  ncRNA- and Pc2 Methylation-Dependent Gene Relocation between Nuclear Structures Mediates Gene Activation Programs , 2011, Cell.

[26]  Thomas Conrad,et al.  Dosage compensation in Drosophila melanogaster: epigenetic fine-tuning of chromosome-wide transcription , 2012, Nature Reviews Genetics.

[27]  P. Becker,et al.  ATP-dependent roX RNA remodeling by the helicase maleless enables specific association of MSL proteins. , 2013, Molecular cell.

[28]  S. Raguz,et al.  Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. , 2010, Molecular cell.

[29]  Brian Burke,et al.  A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells , 2012, The Journal of cell biology.

[30]  M. Daugherty,et al.  A solution to limited genomic capacity: using adaptable binding surfaces to assemble the functional HIV Rev oligomer on RNA. , 2008, Molecular cell.

[31]  C. Danko,et al.  Enhancer transcripts mark active estrogen receptor binding sites , 2013, Genome research.

[32]  Richard A Young,et al.  Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2. , 2010, Molecular cell.

[33]  G. Fink,et al.  Antisense Transcription Controls Cell Fate in Saccharomyces cerevisiae , 2006, Cell.

[34]  Karissa Y. Sanbonmatsu,et al.  Structural architecture of the human long non-coding RNA, steroid receptor RNA activator , 2012, Nucleic acids research.

[35]  M. Hennig,et al.  The arginine-rich RNA-binding motif of HIV-1 Rev is intrinsically disordered and folds upon RRE binding. , 2013, Biophysical journal.

[36]  Seung-Won Park,et al.  An Evolutionarily Conserved Domain of roX2 RNA Is Sufficient for Induction of H4-Lys16 Acetylation on the Drosophila X Chromosome , 2007, Genetics.

[37]  René F. Ketting,et al.  PIWI-interacting RNAs: from generation to transgenerational epigenetics , 2013, Nature Reviews Genetics.

[38]  A. Feinberg,et al.  Loss of imprinting of a paternally expressed transcript, with antisense orientation to KVLQT1, occurs frequently in Beckwith-Wiedemann syndrome and is independent of insulin-like growth factor II imprinting. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[39]  Soichiro Yamanaka,et al.  Mtr4-like Protein Coordinates Nuclear RNA Processing for Heterochromatin Assembly and for Telomere Maintenance , 2013, Cell.

[40]  E. Sánchez-Herrero,et al.  Spatially ordered transcription of regulatory DNA in the bithorax complex of Drosophila. , 1989, Development.

[41]  A. Ferguson-Smith Genomic imprinting: the emergence of an epigenetic paradigm , 2011, Nature Reviews Genetics.

[42]  J. B. Jaynes,et al.  Transcription of bxd Noncoding RNAs Promoted by Trithorax Represses Ubx in cis by Transcriptional Interference , 2006, Cell.

[43]  Yuval Kluger,et al.  PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes. , 2012, Molecular cell.

[44]  L. Steinmetz,et al.  Trans-acting antisense RNAs mediate transcriptional gene cosuppression in S. cerevisiae. , 2009, Genes & development.

[45]  Chris P. Ponting,et al.  Identification and Properties of 1,119 Candidate LincRNA Loci in the Drosophila melanogaster Genome , 2012, Genome biology and evolution.

[46]  D. Tollervey,et al.  A ncRNA modulates histone modification and mRNA induction in the yeast GAL gene cluster. , 2008, Molecular cell.

[47]  Leighton J. Core,et al.  Nascent RNA Sequencing Reveals Widespread Pausing and Divergent Initiation at Human Promoters , 2008, Science.

[48]  Yvonne A. Evrard,et al.  Mediation of CTCF transcriptional insulation by DEAD-box RNA-binding protein p68 and steroid receptor RNA activator SRA. , 2010, Genes & development.

[49]  W. Gilbert Origin of life: The RNA world , 1986, Nature.

[50]  F. Pauler,et al.  Airn Transcriptional Overlap, But Not Its lncRNA Products, Induces Imprinted Igf2r Silencing , 2012, Science.

[51]  B. Cairns The logic of chromatin architecture and remodelling at promoters , 2009, Nature.

[52]  Phillip A. Sharp,et al.  Argonaute-Bound Small RNAs from Promoter-Proximal RNA Polymerase II , 2014, Cell.

[53]  C. Glass,et al.  Induced ncRNAs Allosterically Modify RNA Binding Proteins in cis to Inhibit Transcription , 2008, Nature.

[54]  Howard Y. Chang,et al.  Genome regulation by long noncoding RNAs. , 2012, Annual review of biochemistry.

[55]  Michael F. Lin,et al.  Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals , 2009, Nature.

[56]  G. Hannon RNA interference : RNA , 2002 .

[57]  N. Brockdorff,et al.  The matrix protein hnRNP U is required for chromosomal localization of Xist RNA. , 2010, Developmental cell.

[58]  Wolf Reik,et al.  Co-evolution of X-chromosome inactivation and imprinting in mammals , 2005, Nature Reviews Genetics.

[59]  Ryan K. Dale,et al.  RNAi-independent role for Argonaute2 in CTCF/CP190 chromatin insulator function. , 2011, Genes & development.

[60]  J. Ule,et al.  iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution , 2010, Nature Structural &Molecular Biology.

[61]  Vincent L. Butty,et al.  Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment , 2013, Cell.

[62]  Howard Y. Chang,et al.  Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. , 2011, Molecular cell.

[63]  T. Meehan,et al.  An atlas of active enhancers across human cell types and tissues , 2014, Nature.

[64]  A. Dejean,et al.  Coordinated methyl and RNA binding is required for heterochromatin localization of mammalian HP1α , 2002, EMBO reports.

[65]  Howard Y. Chang,et al.  A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression , 2011, Nature.

[66]  Phillip A. Sharp,et al.  Divergent Transcription: A Driving Force for New Gene Origination? , 2013, Cell.

[67]  Christopher B. Burge,et al.  Promoter directionality is controlled by U1 snRNP and polyadenylation signals , 2013, Nature.

[68]  Robert E. Kingston,et al.  Mechanisms of Polycomb gene silencing: knowns and unknowns , 2009, Nature Reviews Molecular Cell Biology.

[69]  M. Rosenfeld,et al.  LncRNA-Dependent Mechanisms of Androgen Receptor-regulated Gene Activation Programs , 2013, Nature.

[70]  S. Eddy Computational Genomics of Noncoding RNA Genes , 2002, Cell.

[71]  David R. Kelley,et al.  Long noncoding RNAs regulate adipogenesis , 2013, Proceedings of the National Academy of Sciences.

[72]  Howard Y. Chang,et al.  Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes , 2010, Science.

[73]  Jennifer A. Doudna,et al.  DNA interrogation by the CRISPR RNA-guided endonuclease Cas9 , 2014, Nature.

[74]  J. Rinn,et al.  lincRNAs act in the circuitry controlling pluripotency and differentiation , 2011, Nature.

[75]  Pu Zhang,et al.  DNMT1-interacting RNAs block gene specific DNA methylation , 2013, Nature.

[76]  J. Keene,et al.  Advancing the functional utility of PAR-CLIP by quantifying background binding to mRNAs and lncRNAs , 2014, Genome Biology.

[77]  D. Bartel,et al.  lincRNAs: Genomics, Evolution, and Mechanisms , 2013, Cell.

[78]  D. Reinberg,et al.  PRC2 binds to active promoters and contacts nascent RNAs in embryonic stem cells , 2013, Nature Structural &Molecular Biology.

[79]  C. Wahlestedt,et al.  Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation , 2012, Nature Biotechnology.

[80]  Daniel St Johnston,et al.  The art and design of genetic screens: Drosophila melanogaster , 2002, Nature Reviews Genetics.

[81]  D. Hogness,et al.  Novel transcripts from the Ultrabithorax domain of the bithorax complex. , 1987, Genes & development.

[82]  C. Kanduri,et al.  Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1 , 2010, Development.

[83]  P. Stadler,et al.  RNA Maps Reveal New RNA Classes and a Possible Function for Pervasive Transcription , 2007, Science.

[84]  G. Kreiman,et al.  Widespread transcription at neuronal activity-regulated enhancers , 2010, Nature.

[85]  Nadav S. Bar,et al.  Landscape of transcription in human cells , 2012, Nature.

[86]  Howard Y. Chang,et al.  Molecular mechanisms of long noncoding RNAs. , 2011, Molecular cell.

[87]  Youngchang Kim,et al.  Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. , 2003, Genes & development.

[88]  T. Lagrange,et al.  Plant-specific multisubunit RNA polymerase in gene silencing , 2010, Epigenetics.

[89]  L. Steinmetz,et al.  Polyadenylation site–induced decay of upstream transcripts enforces promoter directionality , 2013, Nature Structural &Molecular Biology.

[90]  John N. Hutchinson,et al.  A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains , 2007, BMC Genomics.

[91]  J. Rinn,et al.  Non-coding RNAs as regulators of embryogenesis , 2011, Nature Reviews Genetics.

[92]  K. Struhl Transcriptional noise and the fidelity of initiation by RNA polymerase II , 2007, Nature Structural &Molecular Biology.

[93]  J. Williamson Induced fit in RNA–protein recognition , 2000, Nature Structural Biology.

[94]  E. Canaani,et al.  A Motif within SET-Domain Proteins Binds Single-Stranded Nucleic Acids and Transcribed and Supercoiled DNAs and Can Interfere with Assembly of Nucleosomes , 2005, Molecular and Cellular Biology.

[95]  Sunjong Kwon Single-molecule fluorescence in situ hybridization: Quantitative imaging of single RNA molecules , 2013, BMB reports.

[96]  J. Mattick The Genetic Signatures of Noncoding RNAs , 2009, PLoS genetics.

[97]  Manolis Kellis,et al.  Genome-wide probing of RNA structure reveals active unfolding of mRNA structures in vivo , 2013, Nature.

[98]  D. Reinberg,et al.  CTCF regulates the human p53 gene through direct interaction with its natural antisense transcript, Wrap53 , 2014, Genes & development.

[99]  N. Brockdorff Noncoding RNA and Polycomb recruitment. , 2013, RNA.

[100]  Barbara P. Rattner,et al.  The roX genes encode redundant male‐specific lethal transcripts required for targeting of the MSL complex , 2002, The EMBO journal.

[101]  Justin Demmerle,et al.  Spatial separation of Xist RNA and polycomb proteins revealed by superresolution microscopy , 2014, Proceedings of the National Academy of Sciences.

[102]  C. Hertel,et al.  A role for noncoding transcription in activation of the yeast PHO5 gene , 2007, Proceedings of the National Academy of Sciences.

[103]  Gene W. Yeo,et al.  Divergent Transcription from Active Promoters , 2008, Science.

[104]  L. Steinmetz,et al.  Bidirectional promoters generate pervasive transcription in yeast , 2009, Nature.

[105]  Wilfried Haerty,et al.  Mutations within lncRNAs are effectively selected against in fruitfly but not in human , 2013, Genome Biology.

[106]  J. Darnell,et al.  Structure-function studies of FMRP RGG peptide recognition of an RNA duplex-quadruplex junction , 2011, Nature Structural &Molecular Biology.

[107]  A. Morillon,et al.  A cryptic unstable transcript mediates transcriptional trans-silencing of the Ty1 retrotransposon in S. cerevisiae. , 2008, Genes & development.

[108]  Chris P. Ponting,et al.  Rapid Turnover of Long Noncoding RNAs and the Evolution of Gene Expression , 2012, PLoS genetics.

[109]  W. Bender,et al.  MicroRNAs in the Drosophila bithorax complex. , 2008, Genes & development.

[110]  E. Lander,et al.  The Xist lncRNA Exploits Three-Dimensional Genome Architecture to Spread Across the X Chromosome , 2013, Science.

[111]  J. Steitz,et al.  The Noncoding RNA Revolution—Trashing Old Rules to Forge New Ones , 2014, Cell.

[112]  T. Cech,et al.  The RNA worlds in context. , 2012, Cold Spring Harbor perspectives in biology.

[113]  Wendy A Bickmore,et al.  Nuclear reorganisation and chromatin decondensation are conserved, but distinct, mechanisms linked to Hox gene activation , 2007, Development.

[114]  C. Vonrhein,et al.  Structure of the 30S ribosomal subunit , 2000, Nature.

[115]  D. Spector,et al.  Direct Visualization of the Co-transcriptional Assembly of a Nuclear Body by Noncoding RNAs , 2010, Nature Cell Biology.

[116]  D. Barlow,et al.  Quantitative genetics: Turning up the heat on QTL mapping , 2002, Nature Reviews Genetics.

[117]  Richard Axel,et al.  Genes Expressed in Neurons of Adult Male Drosophila , 1997, Cell.

[118]  Robin D. Dowell,et al.  Toggle involving cis-interfering noncoding RNAs controls variegated gene expression in yeast , 2009, Proceedings of the National Academy of Sciences.

[119]  R. Kingston,et al.  Stabilization of Chromatin Structure by PRC1, a Polycomb Complex , 1999, Cell.

[120]  L. Vasiljeva,et al.  lncRNA recruits RNAi and the exosome to dynamically regulate pho1 expression in response to phosphate levels in fission yeast , 2014, Genes & development.

[121]  C. Glass,et al.  Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation , 2013, Nature.

[122]  J. Rinn,et al.  A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response , 2010, Cell.

[123]  Ana Serra Barros,et al.  Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript , 2007, Nature.

[124]  Nicholas T. Ingolia,et al.  Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes , 2011, Cell.

[125]  T. Hughes,et al.  Most “Dark Matter” Transcripts Are Associated With Known Genes , 2010, PLoS biology.

[126]  D. Reinberg,et al.  Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin. , 2014, Molecular cell.

[127]  Lothar Schermelleh,et al.  RecA bundles mediate homology pairing between distant sisters during DNA break repair , 2013, Nature.

[128]  C. Dean,et al.  Cold-induced silencing by long antisense transcripts of an Arabidopsis Polycomb target , 2009, Nature.

[129]  F. Crick Origin of the Genetic Code , 1967, Nature.

[130]  David G. Knowles,et al.  The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression , 2012, Genome research.

[131]  William Stafford Noble,et al.  Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project , 2007, Nature.

[132]  Wolfgang Huber,et al.  A high-resolution map of transcription in the yeast genome. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[133]  Robert A. Martienssen,et al.  RNA interference in the nucleus: roles for small RNAs in transcription, epigenetics and beyond , 2013, Nature Reviews Genetics.

[134]  S. Loeillet,et al.  XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast , 2011, Nature.

[135]  J. Ragoussis,et al.  A Large Fraction of Extragenic RNA Pol II Transcription Sites Overlap Enhancers , 2010, PLoS biology.

[136]  G. Natoli,et al.  Noncoding transcription at enhancers: general principles and functional models. , 2012, Annual review of genetics.

[137]  V. Corces,et al.  RNA interference machinery influences the nuclear organization of a chromatin insulator , 2006, Nature Genetics.

[138]  M. Daugherty,et al.  Structural basis for cooperative RNA binding and export complex assembly by HIV Rev , 2010, Nature Structural &Molecular Biology.

[139]  Jeannie T. Lee,et al.  Jpx RNA Activates Xist by Evicting CTCF , 2013, Cell.

[140]  R. Kingston,et al.  The Core of the Polycomb Repressive Complex Is Compositionally and Functionally Conserved in Flies and Humans , 2002, Molecular and Cellular Biology.

[141]  A. Wierzbicki,et al.  A SWI/SNF Chromatin-Remodeling Complex Acts in Noncoding RNA-Mediated Transcriptional Silencing , 2013, Molecular cell.

[142]  David A. Orlando,et al.  Mediator and Cohesin Connect Gene Expression and Chromatin Architecture , 2010, Nature.

[143]  Jeannie T. Lee Epigenetic Regulation by Long Noncoding RNAs , 2012, Science.

[144]  C. Spillane,et al.  Epigenetic mechanisms underlying genomic imprinting in plants. , 2012, Annual review of plant biology.

[145]  Ronald L. Davis,et al.  roX1 RNA Paints the X Chromosome of Male Drosophila and Is Regulated by the Dosage Compensation System , 1997, Cell.

[146]  Jeannie T. Lee,et al.  X-Inactivation, Imprinting, and Long Noncoding RNAs in Health and Disease , 2013, Cell.

[147]  Howard Y. Chang,et al.  Essential role of lncRNA binding for WDR5 maintenance of active chromatin and embryonic stem cell pluripotency , 2014, eLife.

[148]  D. Reinberg,et al.  The Polycomb complex PRC2 and its mark in life , 2011, Nature.

[149]  A. Jacquier The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs , 2009, Nature Reviews Genetics.

[150]  Mark Bates,et al.  Super-resolution fluorescence microscopy. , 2009, Annual review of biochemistry.

[151]  D. Reinberg,et al.  Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA. , 2010, Genes & development.

[152]  R. Lehmann,et al.  A Noncoding RNA Is Required for the Repression of RNApolII-Dependent Transcription in Primordial Germ Cells , 2004, Current Biology.

[153]  V. Corces,et al.  CTCF: Master Weaver of the Genome , 2009, Cell.

[154]  L. Cozzuto,et al.  Nonoverlapping functions of the Polycomb group Cbx family of proteins in embryonic stem cells. , 2012, Cell stem cell.

[155]  Lars M. Steinmetz,et al.  Set3 HDAC Mediates Effects of Overlapping Noncoding Transcription on Gene Induction Kinetics , 2012, Cell.

[156]  Jennifer A. Mitchell,et al.  The Air Noncoding RNA Epigenetically Silences Transcription by Targeting G9a to Chromatin , 2008, Science.

[157]  R. Shiekhattar,et al.  Activating RNAs associate with Mediator to enhance chromatin architecture and transcription , 2013, Nature.

[158]  Huan Wang,et al.  Genome-wide identification of long noncoding natural antisense transcripts and their responses to light in Arabidopsis , 2014, Genome research.

[159]  D. Spector,et al.  Nuclear neighborhoods and gene expression. , 2009, Current opinion in genetics & development.

[160]  Markus Blatter,et al.  RNA recognition motifs: boring? Not quite. , 2008, Current opinion in structural biology.

[161]  Gerald M Rubin,et al.  Identification of putative noncoding polyadenylated transcripts in Drosophila melanogaster. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[162]  Michael Primig,et al.  Transcription of Two Long Noncoding RNAs Mediates Mating-Type Control of Gametogenesis in Budding Yeast , 2012, Cell.

[163]  C. Pikaard,et al.  RNA Polymerase V transcription guides ARGONAUTE4 to chromatin , 2009, Nature Genetics.

[164]  Frank Grützner,et al.  The evolution of lncRNA repertoires and expression patterns in tetrapods , 2014, Nature.

[165]  N. Chua,et al.  Genome-Wide Analysis Uncovers Regulation of Long Intergenic Noncoding RNAs in Arabidopsis[C][W] , 2012, Plant Cell.

[166]  I. Grummt,et al.  Interaction of noncoding RNA with the rDNA promoter mediates recruitment of DNMT3b and silencing of rRNA genes. , 2010, Genes & development.

[167]  C. Allis,et al.  Mouse Polycomb Proteins Bind Differentially to Methylated Histone H3 and RNA and Are Enriched in Facultative Heterochromatin , 2006, Molecular and Cellular Biology.

[168]  C. Glass,et al.  Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription , 2013, Nature.

[169]  C. Ponting,et al.  Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs. , 2007, Genome research.

[170]  J. Mcneil,et al.  XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure , 1996, The Journal of cell biology.

[171]  Howard Y. Chang,et al.  Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs , 2007, Cell.

[172]  T. Cech,et al.  Promiscuous RNA binding by Polycomb Repressive Complex 2 , 2013, Nature Structural &Molecular Biology.

[173]  S. Razin,et al.  A requiem to the nuclear matrix: from a controversial concept to 3D organization of the nucleus , 2014, Chromosoma.

[174]  Jeannie T. Lee,et al.  Polycomb Proteins Targeted by a Short Repeat RNA to the Mouse X Chromosome , 2008, Science.

[175]  D. Bartel,et al.  Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution , 2011, Cell.

[176]  David R. Kelley,et al.  Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre , 2014, Nature Structural &Molecular Biology.

[177]  T. Shibata,et al.  Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs , 2008, Nature.

[178]  R. Breaker,et al.  In-line probing analysis of riboswitches. , 2008, Methods in molecular biology.

[179]  Eugene Bolotin,et al.  The noncoding RNA Mistral activates Hoxa6 and Hoxa7 expression and stem cell differentiation by recruiting MLL1 to chromatin. , 2011, Molecular cell.

[180]  Tilman Sanchez-Elsner,et al.  Noncoding RNAs of Trithorax Response Elements Recruit Drosophila Ash1 to Ultrabithorax , 2006, Science.

[181]  Cole Trapnell,et al.  Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. , 2011, Genes & development.

[182]  K. Weeks,et al.  RNA structure analysis at single nucleotide resolution by selective 2'-hydroxyl acylation and primer extension (SHAPE). , 2005, Journal of the American Chemical Society.

[183]  Sarah K. Bowman,et al.  High-resolution Xist binding maps reveal 2-step spreading during X-inactivation , 2013, Nature.

[184]  Daniel Schulz,et al.  Transcriptome Surveillance by Selective Termination of Noncoding RNA Synthesis , 2013, Cell.

[185]  Rolf Backofen,et al.  Tandem stem-loops in roX RNAs act together to mediate X chromosome dosage compensation in Drosophila. , 2013, Molecular cell.

[186]  C. Dean,et al.  Vernalization – a cold-induced epigenetic switch , 2012, Journal of Cell Science.

[187]  Sibum Sung,et al.  Vernalization-Mediated Epigenetic Silencing by a Long Intronic Noncoding RNA , 2011, Science.

[188]  Fred Winston,et al.  Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene , 2004, Nature.

[189]  Le Cong,et al.  Multiplex Genome Engineering Using CRISPR/Cas Systems , 2013, Science.

[190]  Sanjay Tyagi,et al.  Single molecule imaging of RNA in situ. , 2011, Methods in molecular biology.