MicroRNA function: multiple mechanisms for a tiny RNA?

MicroRNAs are sequence-specific regulators of post-transcriptional gene expression in many eukaryotes. They are believed to control the expression of thousands of target mRNAs, with each mRNA believed to be targeted by multiple microRNAs. Recent studies have uncovered various mechanisms by which microRNAs down-regulate their target mRNAs and have linked a well-known subcellular structure, the cytoplasmic processing bodies (PBs) to the microRNA pathway. The finding that microRNAs are misexpressed in cancers has reinforced the idea that their regulatory roles are very important.

[1]  Haiwei Song,et al.  The enzymes and control of eukaryotic mRNA turnover , 2004, Nature Structural &Molecular Biology.

[2]  Qinghua Liu,et al.  Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophila. , 2005, Genes & development.

[3]  Yong Zhao,et al.  Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis , 2005, Nature.

[4]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[5]  D. Bartel,et al.  Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs , 2004, Nature Reviews Genetics.

[6]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[7]  D. Barford,et al.  Structural insights into mRNA recognition from a PIWI domain–siRNA guide complex , 2005, Nature.

[8]  Artemis G Hatzigeorgiou,et al.  miRNP:mRNA association in polyribosomes in a human neuronal cell line. , 2004, RNA.

[9]  Gary Ruvkun,et al.  Identification of many microRNAs that copurify with polyribosomes in mammalian neurons , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Elisa Izaurralde,et al.  Decay of mRNAs targeted by RISC requires XRN1, the Ski complex, and the exosome. , 2005, RNA.

[11]  E. Lai.  Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation , 2002, Nature Genetics.

[12]  Anne Gatignol,et al.  TRBP, a regulator of cellular PKR and HIV‐1 virus expression, interacts with Dicer and functions in RNA silencing , 2005, EMBO reports.

[13]  E. Moss,et al.  Two genetic circuits repress the Caenorhabditis elegans heterochronic gene lin-28 after translation initiation. , 2002, Developmental biology.

[14]  Erik J. Sontheimer,et al.  Assembly and function of RNA silencing complexes , 2005, Nature Reviews Molecular Cell Biology.

[15]  Roy Parker,et al.  Movement of Eukaryotic mRNAs Between Polysomes and Cytoplasmic Processing Bodies , 2005, Science.

[16]  R. Heintzmann,et al.  A role for eIF4E and eIF4E-transporter in targeting mRNPs to mammalian processing bodies. , 2005, RNA.

[17]  J. M. Thomson,et al.  Argonaute2 Is the Catalytic Engine of Mammalian RNAi , 2004, Science.

[18]  P. Mantica,et al.  The Decay of , 2000 .

[19]  S. Ding,et al.  Induction and Suppression of RNA Silencing by an Animal Virus , 2002, Science.

[20]  E. Chan,et al.  GW182 is critical for the stability of GW bodies expressed during the cell cycle and cell proliferation , 2004, Journal of Cell Science.

[21]  G. Hannon,et al.  Crystal Structure of Argonaute and Its Implications for RISC Slicer Activity , 2004, Science.

[22]  J. Castle,et al.  Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs , 2005, Nature.

[23]  Konstantin Khrapko,et al.  A microRNA array reveals extensive regulation of microRNAs during brain development. , 2003, RNA.

[24]  G. Hutvagner,et al.  A microRNA in a Multiple-Turnover RNAi Enzyme Complex , 2002, Science.

[25]  Min Han,et al.  The developmental timing regulator AIN-1 interacts with miRISCs and may target the argonaute protein ALG-1 to cytoplasmic P bodies in C. elegans. , 2005, Molecular cell.

[26]  Roy Parker,et al.  Eukaryotic mRNA decapping. , 2004, Annual review of biochemistry.

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

[28]  S. Tenenbaum,et al.  A phosphorylated cytoplasmic autoantigen, GW182, associates with a unique population of human mRNAs within novel cytoplasmic speckles. , 2002, Molecular biology of the cell.

[29]  W. Filipowicz,et al.  RNAi: The Nuts and Bolts of the RISC Machine , 2005, Cell.

[30]  Roy Parker,et al.  Decapping and Decay of Messenger RNA Occur in Cytoplasmic Processing Bodies , 2003 .

[31]  Kuniaki Saito,et al.  Processing of Pre-microRNAs by the Dicer-1–Loquacious Complex in Drosophila Cells , 2005, PLoS biology.

[32]  S. Lowe,et al.  A microRNA polycistron as a potential human oncogene , 2005, Nature.

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

[34]  H. Lipkin.  Where is the ?c? , 1978 .

[35]  H. Blau,et al.  Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies , 2005, Nature Cell Biology.

[36]  Randal J. Kaufman,et al.  Stress granules and processing bodies are dynamically linked sites of mRNP remodeling , 2005, The Journal of cell biology.

[37]  B. Séraphin,et al.  The GW182 protein colocalizes with mRNA degradation associated proteins hDcp1 and hLSm4 in cytoplasmic GW bodies. , 2003, RNA.

[38]  D. Barford,et al.  Crystal structure of a PIWI protein suggests mechanisms for siRNA recognition and slicer activity , 2004, The EMBO journal.

[39]  N. Rajewsky,et al.  A pancreatic islet-specific microRNA regulates insulin secretion , 2004, Nature.

[40]  W. Filipowicz,et al.  Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesis. , 2004, RNA.

[41]  Michael Q. Zhang,et al.  The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. , 2002, Genes & development.

[42]  R. Wagner,et al.  A chemical modification method for the structural analysis of RNA and RNA-protein complexes within living cells. , 1998, Analytical biochemistry.

[43]  V. Ambros,et al.  MicroRNA Pathways in Flies and Worms Growth, Death, Fat, Stress, and Timing , 2003, Cell.

[44]  T. Rana,et al.  siRNA function in RNAi: a chemical modification analysis. , 2003, RNA.

[45]  B. Reinhart,et al.  The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans , 2000, Nature.

[46]  W. Filipowicz,et al.  Inhibition of Translational Initiation by Let-7 MicroRNA in Human Cells , 2005, Science.

[47]  R. Russell,et al.  bantam Encodes a Developmentally Regulated microRNA that Controls Cell Proliferation and Regulates the Proapoptotic Gene hid in Drosophila , 2003, Cell.

[48]  V. Ambros,et al.  The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. , 1999, Developmental biology.

[49]  Jean-Marie Buerstedde,et al.  A Mouse Cytoplasmic Exoribonuclease (mXRN1p) with Preference for G4 Tetraplex Substrates , 1997, The Journal of cell biology.

[50]  Thomas Tuschl,et al.  Structural basis for 5′-end-specific recognition of guide RNA by the A. fulgidus Piwi protein , 2005, Nature.

[51]  A. Denli,et al.  Normal microRNA Maturation and Germ-Line Stem Cell Maintenance Requires Loquacious, a Double-Stranded RNA-Binding Domain Protein , 2005, PLoS biology.

[52]  A. Saïb,et al.  A Cellular MicroRNA Mediates Antiviral Defense in Human Cells , 2005, Science.

[53]  G. Ruvkun,et al.  Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans , 1993, Cell.

[54]  T. Tuschl,et al.  Mechanisms of gene silencing by double-stranded RNA , 2004, Nature.

[55]  Ji-Joon Song,et al.  Purified Argonaute2 and an siRNA form recombinant human RISC , 2005, Nature Structural &Molecular Biology.

[56]  R. Parker,et al.  Processing bodies require RNA for assembly and contain nontranslating mRNAs. , 2005, RNA.

[57]  D. Bartel,et al.  MicroRNA-Directed Cleavage of HOXB8 mRNA , 2004, Science.

[58]  T. Tuschl,et al.  Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate , 2001, The EMBO journal.

[59]  C. Croce,et al.  miR-15 and miR-16 induce apoptosis by targeting BCL2. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[60]  Kathryn A. O’Donnell,et al.  c-Myc-regulated microRNAs modulate E2F1 expression , 2005, Nature.

[61]  R. Plasterk,et al.  Substrate requirements for let-7 function in the developing zebrafish embryo. , 2004, Nucleic acids research.

[62]  N. Sonenberg,et al.  A New Paradigm for Translational Control: Inhibition via 5′-3′ mRNA Tethering by Bicoid and the eIF4E Cognate 4EHP , 2005, Cell.

[63]  H. Horvitz,et al.  MicroRNA expression profiles classify human cancers , 2005, Nature.

[64]  M. Carmell,et al.  Posttranscriptional Gene Silencing in Plants , 2006 .

[65]  Phillip A Sharp,et al.  siRNAs can function as miRNAs , 2003 .

[66]  Shuang Huang,et al.  Involvement of MicroRNA in AU-Rich Element-Mediated mRNA Instability , 2005, Cell.

[67]  A. Pasquinelli,et al.  Regulation by let-7 and lin-4 miRNAs Results in Target mRNA Degradation , 2005, Cell.

[68]  Isabelle Behm-Ansmant,et al.  A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing. , 2005, RNA.

[69]  T. Tuschl,et al.  Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. , 2004, Molecular cell.

[70]  B. Cullen,et al.  MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[71]  Phillip D Zamore,et al.  Perspective: machines for RNAi. , 2005, Genes & development.

[72]  V. Kim.  MicroRNA biogenesis: coordinated cropping and dicing , 2005, Nature Reviews Molecular Cell Biology.

[73]  P. Zamore,et al.  Kinetic analysis of the RNAi enzyme complex , 2004, Nature Structural &Molecular Biology.

[74]  Michael Sattler,et al.  Novel modes of protein-RNA recognition in the RNAi pathway. , 2005, Current opinion in structural biology.

[75]  M. Hentze,et al.  Tethered-function analysis reveals that elF4E can recruit ribosomes independent of its binding to the cap structure. , 2001, RNA.

[76]  R. Aharonov,et al.  Identification of hundreds of conserved and nonconserved human microRNAs , 2005, Nature Genetics.

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