RNA and transcriptional modulation of gene expression

The roles that RNA molecules play in the regulation of gene expression have only recently become apparent. Recent work in this area has uncovered several complex, RNA-mediated networks of gene regulation in eukaryotic systems. One newly discovered mechanism of RNA mediated gene regulation takes place at the level of transcription. In yeast, plant, and mammalian systems, small RNAs targeted to gene promoters can result in a repression of transcription. Small RNA mediated transcriptional silencing has been shown to be operative by changes in chromatin structure at the targeted promoter. Specifically, silencing has been observed to correlate with decreases in certain active-state histone modifications, increases in various silent state histone methylation marks, and in some instances, DNA methylation at the targeted promoter. These epigenetic remodeling events represent a more stable, heritable form of gene regulation as opposed to the transitory post-transcriptional regulation observed in traditional RNAi mechanisms. Several recent findings have shed light on this newly discovered link between small RNA molecules and epigenetic regulatory machinery, notably in human cells.

[1]  K. Morris,et al.  An RNA targeted to the HIV-1 LTR promoter modulates indiscriminate off-target gene activation , 2007, Nucleic acids research.

[2]  K. Morris,et al.  Promoter-associated RNA is required for RNA-directed transcriptional gene silencing in human cells , 2007, Proceedings of the National Academy of Sciences.

[3]  Yukihide Tomari,et al.  piRNAs--the ancient hunters of genome invaders. , 2007, Genes & development.

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

[5]  J. Mattick A new paradigm for developmental biology , 2007, Journal of Experimental Biology.

[6]  Michael B. Stadler,et al.  Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome , 2007, Nature Genetics.

[7]  Robert A. Martienssen,et al.  Noncoding RNAs and Gene Silencing , 2007, Cell.

[8]  G. Finocchiaro,et al.  Localizing hotspots of antisense transcription , 2007, Nucleic acids research.

[9]  D. Corey,et al.  Activating gene expression in mammalian cells with promoter-targeted duplex RNAs. , 2007, Nature chemical biology.

[10]  J. Timmons,et al.  Does everything now make (anti)sense? , 2006, Biochemical Society transactions.

[11]  R. Place,et al.  Small dsRNAs induce transcriptional activation in human cells , 2006, Proceedings of the National Academy of Sciences.

[12]  D. Corey,et al.  Involvement of AGO1 and AGO2 in mammalian transcriptional silencing , 2006, Nature Structural &Molecular Biology.

[13]  John J Rossi,et al.  Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells , 2006, Nature Structural &Molecular Biology.

[14]  N. Tolia,et al.  Argonaute Slicing Is Required for Heterochromatic Silencing and Spreading , 2006, Science.

[15]  R. Plasterk,et al.  Gene expression: Long-term gene silencing by RNAi , 2006, Nature.

[16]  J. Mattick,et al.  Non-coding RNA. , 2006, Human molecular genetics.

[17]  R. Carthew Gene regulation by microRNAs. , 2006, Current opinion in genetics & development.

[18]  Jun Kawai,et al.  Clusters of Internally Primed Transcripts Reveal Novel Long Noncoding RNAs , 2006, PLoS genetics.

[19]  A. Riggs,et al.  The antisense strand of small interfering RNAs directs histone methylation and transcriptional gene silencing in human cells. , 2005, RNA.

[20]  P. Sharp,et al.  Function and localization of microRNAs in mammalian cells. , 2006, Cold Spring Harbor symposia on quantitative biology.

[21]  K. Morris siRNA-mediated transcriptional gene silencing: the potential mechanism and a possible role in the histone code , 2005, Cellular and Molecular Life Sciences CMLS.

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

[23]  P. Sarnow,et al.  Modulation of Hepatitis C Virus RNA Abundance by a Liver-Specific MicroRNA , 2005, Science.

[24]  T. Hughes,et al.  A systematic search for new mammalian noncoding RNAs indicates little conserved intergenic transcription , 2005, BMC Genomics.

[25]  R. Shiekhattar,et al.  TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing , 2005, Nature.

[26]  D. Corey,et al.  Inhibiting gene expression at transcription start sites in chromosomal DNA with antigene RNAs , 2005, Nature chemical biology.

[27]  R. Martienssen,et al.  RNA Polymerase II Is Required for RNAi-Dependent Heterochromatin Assembly , 2005, Science.

[28]  J. Rossi,et al.  Short hairpin RNA-directed cytosine (CpG) methylation of the RASSF1A gene promoter in HeLa cells. , 2005, Molecular therapy : the journal of the American Society of Gene Therapy.

[29]  Gregory J. Hannon,et al.  MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies , 2005, Nature Cell Biology.

[30]  G. Macino,et al.  Small Interfering RNAs That Trigger Posttranscriptional Gene Silencing Are Not Required for the Histone H3 Lys9 Methylation Necessary for Transgenic Tandem Repeat Stabilization in Neurospora crassa , 2005, Molecular and Cellular Biology.

[31]  G. Wang,et al.  Cytoplasmic and Nuclear Retained DMPK mRNAs Are Targets for RNA Interference in Myotonic Dystrophy Cells* , 2005, Journal of Biological Chemistry.

[32]  P. Sharp,et al.  Transcriptional silencing of a transgene by RNAi in the soma of C. elegans. , 2005, Genes & development.

[33]  D. Bushnell,et al.  Structural basis of eukaryotic gene transcription , 2005, FEBS letters.

[34]  T. Rana,et al.  Specific and potent RNAi in the nucleus of human cells , 2005, Nature Structural &Molecular Biology.

[35]  C. Steer,et al.  Double-stranded siRNA targeted to the huntingtin gene does not induce DNA methylation. , 2004, Biochemical and biophysical research communications.

[36]  K. Morris,et al.  Small Interfering RNA-Induced Transcriptional Gene Silencing in Human Cells , 2004, Science.

[37]  W. Filipowicz,et al.  Lack of homologous sequence-specific DNA methylation in response to stable dsRNA expression in mouse oocytes. , 2004, Nucleic acids research.

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

[39]  Peter A. Jones,et al.  Epigenetics in human disease and prospects for epigenetic therapy , 2004, Nature.

[40]  Yi Zhang,et al.  The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3. , 2004, Current opinion in genetics & development.

[41]  R. Martienssen,et al.  Distinct Mechanisms Determine Transposon Inheritance and Methylation via Small Interfering RNA and Histone Modification , 2003, PLoS biology.

[42]  B. Li,et al.  Expression profiling reveals off-target gene regulation by RNAi , 2003, Nature Biotechnology.

[43]  Kuang-Hung Cheng,et al.  Histone Deacetylases: Unique Players in Shaping the Epigenetic Histone Code , 2003, Annals of the New York Academy of Sciences.

[44]  Xiaofeng Cao,et al.  ARGONAUTE4 Control of Locus-Specific siRNA Accumulation and DNA and Histone Methylation , 2003, Science.

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

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

[47]  Hengbin Wang,et al.  Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing , 2002, Science.

[48]  Ira M. Hall,et al.  Regulation of Heterochromatic Silencing and Histone H3 Lysine-9 Methylation by RNAi , 2002, Science.

[49]  Phillip D Zamore,et al.  RNAi: nature abhors a double-strand. , 2002, Current opinion in genetics & development.

[50]  J. Birchler,et al.  RNAi related mechanisms affect both transcriptional and posttranscriptional transgene silencing in Drosophila. , 2002, Molecular cell.

[51]  K. Nishikura,et al.  A Short Primer on RNAi RNA-Directed RNA Polymerase Acts as a Key Catalyst , 2001, Cell.

[52]  C. Allis,et al.  Translating the Histone Code , 2001, Science.

[53]  A. Pasquinelli,et al.  Genes and Mechanisms Related to RNA Interference Regulate Expression of the Small Temporal RNAs that Control C. elegans Developmental Timing , 2001, Cell.

[54]  H. Vaucheret,et al.  AGO1, QDE-2, and RDE-1 are related proteins required for post-transcriptional gene silencing in plants, quelling in fungi, and RNA interference in animals. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[55]  M. Matzke,et al.  Transcriptional silencing and promoter methylation triggered by double‐stranded RNA , 2000, The EMBO journal.

[56]  A. Villeneuve,et al.  Transgene-mediated cosuppression in the C. elegans germ line. , 2000, Genes & development.

[57]  Ronald H. A. Plasterk,et al.  A genetic link between co-suppression and RNA interference in C. elegans , 2000, Nature.

[58]  C. Allis,et al.  The language of covalent histone modifications , 2000, Nature.

[59]  D. Haber,et al.  DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development , 1999, Cell.

[60]  Andrew Fire,et al.  The rde-1 Gene, RNA Interference, and Transposon Silencing in C. elegans , 1999, Cell.

[61]  A. Fire,et al.  RNA as a target of double-stranded RNA-mediated genetic interference in Caenorhabditis elegans. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[62]  A. Fire,et al.  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans , 1998, Nature.

[63]  H. L. Sänger,et al.  RNA-directed de novo methylation of genomic sequences in plants , 1994, Cell.

[64]  G. Macino,et al.  Quelling: transient inactivation of gene expression in Neurospora crassa by transformation with homologous sequences , 1992, Molecular microbiology.

[65]  M. Primig,et al.  Reversible methylation and inactivation of marker genes in sequentially transformed tobacco plants , 1989, The EMBO journal.

[66]  T. Cech The chemistry of self-splicing RNA and RNA enzymes. , 1987, Science.