miRNAs on the move: miRNA biogenesis and the RNAi machinery

Current Opinion in Cell Biology

Volumn 16, Issue 3, 2004, Pages 223-229

  Murchison, Elizabeth P ^a   Hannon, Gregory J ^a  

^a Simons Center for Quantitative Biology   (United States)

Author keywords

dFMR1; double stranded RNA; Drosophila fragile X mental retardation protein; dsRNA; embryonic stem; ES; FMRP; fragile X mental retardation protein; micro RNA; miRNA; nt; nucleotide; pre miRNA; precursor miRNA; pri miRNA; primary miRNA; RISC

Indexed keywords

ARGININE; CALRETICULIN; ENZYME; EXPORTIN 5; HELICASE; LYSINE; MICRORNA; PROLINE; RIBONUCLEASE III; RIBONUCLEOPROTEIN; RNA HELICASE; RNA POLYMERASE; SMALL INTERFERING RNA; UNCLASSIFIED DRUG;

ALGORITHM; B LYMPHOCYTE; BIOGENESIS; CELL LINE; CELL NUCLEUS; CELL VIABILITY; CENTROMERE; CISTRON; CYTOSOLIC FRACTION; DNA CLEAVAGE; DROSOPHILA; ENZYME METABOLISM; GENE CLUSTER; GENE MUTATION; GENE SILENCING; GENETIC TRANSCRIPTION; HETEROCHROMATIN; IMMUNOPRECIPITATION; MENTAL DEFICIENCY; MOLECULAR CLONING; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REVIEW; RNA ANALYSIS; RNA BINDING; RNA INTERFERENCE; RNA PROCESSING; RNA STRUCTURE; RNA TRANSLATION; SYNAPTOGENESIS; TISSUE SPECIFICITY; TRANSGENE;

ANIMALS; CELL NUCLEUS; CYTOPLASM; HUMANS; MICRORNAS; RNA INTERFERENCE; RNA TRANSPORT; RNA-INDUCED SILENCING COMPLEX;

EID: 2342485506     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ceb.2004.04.003     Document Type: Review

References (77)

1. Hannon G.J. RNA interference. Nature. 418:2002;244-251
2. Fire A., Xu S., Montgomery M.K., Kostas S.A., Driver S.E., Mello C.C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 391:1998;806-811
3. Grishok A., Pasquinelli A.E., Conte D., Li N., Parrish S., Ha I., Baillie D.L., Fire A., Ruvkun G., Mello C.C. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell. 106:2001;23-34
4. Lee R.C., Feinbaum R.L., Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 75:1993;843-854
5. Reinhart B.J., Slack F.J., Basson M., Pasquinelli A.E., Bettinger J.C., Rougvie A.E., Horvitz H.R., Ruvkun G. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 403:2000;901-906
6. Vella M.C., Choi E.Y., Lin S.Y., Reinert K., Slack F.J. The C. elegans microRNA let-7 binds to imperfect let-7 complementary sites from the lin-41 3′UTR. Genes Dev. 18:2004;132-137
7. Kidner C.A., Martienssen R.A. Spatially restricted microRNA directs leaf polarity through ARGONAUTE1. Nature. 428:2004;81-84
8. Johnston R.J., Hobert O. A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature. 426:2003;845-849
9. Aukerman M.J., Sakai H. Regulation of flowering time and floral organ identity by a MicroRNA and its APETALA2-like target genes. Plant Cell. 15:2003;2730-2741
10. Palatnik J.F., Allen E., Wu X., Schommer C., Schwab R., Carrington J.C., Weigel D. Control of leaf morphogenesis by microRNAs. Nature. 425:2003;257-263
11. Brennecke J., Hipfner D.R., Stark A., Russell R.B., Cohen S.M. bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 113:2003;25-36
12. •].
13. •].
14. •].
15. •] describe the first algorithms for predicting miRNA targets in a number of organisms. While many plant miRNA genes are found to be almost perfectly complementary with their predicted targets, animal miRNA:target pairs have limited complementarity. Some experimental evidence is presented to back up the in silico predictions. While in plants developmental transcription factors are over-represented in the group of predicted miRNA targets, in animals many classes of transcripts appear to be regulated by miRNAs.
16. Lee Y., Jeon K., Lee J.T., Kim S., Kim V.N. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 21:2002;4663-4670
17. Houbaviy H.B., Murray M.F., Sharp P.A. Embryonic stem cell-specific MicroRNAs. Dev Cell. 5:2003;351-358 The authors clone miRNAs from differentiated and undifferentiated murine embryonic stem (ES) cells and characterize a new cluster of miRNAs which appear to be specific to undifferentiated ES cells. This study demonstrates that the regulation of miRNA genes is surprisingly dynamic and tissue-compartmentalized.
18. Lagos-Quintana M., Rauhut R., Yalcin A., Meyer J., Lendeckel W., Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol. 12:2002;735-739
19. Dostie J., Mourelatos Z., Yang M., Sharma A., Dreyfuss G. Numerous microRNPs in neuronal cells containing novel microRNAs. RNA. 9:2003;180-186
20. Krichevsky A.M., King K.S., Donahue C.P., Khrapko K., Kosik K.S. A microRNA array reveals extensive regulation of microRNAs during brain development. RNA. 9:2003;1274-1281
21. Moss E.G., Tang L. Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites. Dev Biol. 258:2003;432-442
22. Lagos-Quintana M., Rauhut R., Lendeckel W., Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 294:2001;853-858
23. Lau N.C., Lim L.P., Weinstein E.G., Bartel D.P. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science. 294:2001;858-862
24. Lee R.C., Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science. 294:2001;862-864
25. Mourelatos Z., Dostie J., Paushkin S., Sharma A., Charroux B., Abel L., Rappsilber J., Mann M., Dreyfuss G. miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev. 16:2002;720-728 The authors isolate a protein complex containing mammalian EIF2C2/Ago2, miRNAs and two SMN-interacting proteins, gemin3 and gemin4. The complex links miRNAs with other aspects of RNA metabolism, as the SMN complex is involved in the organization of various RNP particles.
26. Lee Y., Ahn C., Han J., Choi H., Kim J., Yim J., Lee J., Provost P., Radmark O., Kim S., et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 425:2003;415-419 Drosha is shown to be responsible for catalyzing the cleavage of pri-miRNA transcripts into miRNA precursors. The realization that miRNAs are preprocessed by a nuclear RNaseIII enzyme, and therefore possess the characteristic 3′ overhang left by RNaseIII enzymes provides a hypothesis for Dicer substrate selection.
27. Fortin K.R., Nicholson R.H., Nicholson A.W. Mouse ribonuclease III. cDNA structure, expression analysis, and chromosomal location. BMC Genomics. 3:2002;26
28. Filippov V., Solovyev V., Filippova M., Gill S.S. A novel type of RNase III family proteins in eukaryotes. Gene. 245:2000;213-221
29. Wu H., Xu H., Miraglia L.J., Crooke S.T. Human RNase III is a 160-kDa protein involved in preribosomal RNA processing. J Biol Chem. 275:2000;36957-36965
30. Blaszczyk J., Tropea J.E., Bubunenko M., Routzahn K.M., Waugh D.S., Court D.L., Ji X. Crystallographic and modeling studies of RNase III suggest a mechanism for double-stranded RNA cleavage. Structure (Camb). 9:2001;1225-1236
31. Papp I., Mette M.F., Aufsatz W., Daxinger L., Schauer S.E., Ray A., van der Winden J., Matzke M., Matzke A.J. Evidence for nuclear processing of plant micro RNA and short interfering RNA precursors. Plant Physiol. 132:2003;1382-1390
32. Provost P., Silverstein R.A., Dishart D., Walfridsson J., Djupedal I., Kniola B., Wright A., Samuelsson B., Radmark O., Ekwall K. Dicer is required for chromosome segregation and gene silencing in fission yeast cells. Proc Natl Acad Sci U S A. 99:2002;16648-16653
33. •].
34. •].
35. •] show that miRNA precursors are exported from the nucleus by Exportin-5. This not only defines a key step in miRNA biogenesis, but also suggests the possibility that miRNAs could be regulated at the level of nuclear export.
36. Gwizdek C., Ossareh-Nazari B., Brownawell A.M., Evers S., Macara I.G., Dargemont C. Minihelix-containing RNAs mediate exportin-5-dependent nuclear export of the double-stranded RNA-binding protein ILF3. J Biol Chem. 279:2004;884-891
37. Findley S.D., Tamanaha M., Clegg N.J., Ruohola-Baker H. Maelstrom, a Drosophila spindle-class gene, encodes a protein that colocalizes with Vasa and RDE1/AGO1 homolog, Aubergine, in nuage. Development. 130:2003;859-871
38. Billy E., Brondani V., Zhang H., Muller U., Filipowicz W. Specific interference with gene expression induced by long, double-stranded RNA in mouse embryonal teratocarcinoma cell lines. Proc Natl Acad Sci U S A. 98:2001;14428-14433
39. Provost P., Dishart D., Doucet J., Frendewey D., Samuelsson B., Radmark O. Ribonuclease activity and RNA binding of recombinant human Dicer. EMBO J. 21:2002;5864-5874
40. Bernstein E., Caudy A.A., Hammond S.M., Hannon G.J. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 409:2001;363-366
41. Ketting R.F., Fischer S.E., Bernstein E., Sijen T., Hannon G.J., Plasterk R.H. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev. 15:2001;2654-2659
42. Knight S.W., Bass B.L. A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science. 293:2001;2269-2271
43. Hutvagner G., McLachlan J., Pasquinelli A.E., Balint E., Tuschl T., Zamore P.D. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 293:2001;834-838
44. Nicholson R.H., Nicholson A.W. Molecular characterization of a mouse cDNA encoding Dicer, a ribonuclease III ortholog involved in RNA interference. Mamm Genome. 13:2002;67-73
45. Zhang H., Kolb F.A., Brondani V., Billy E., Filipowicz W. Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP. EMBO J. 21:2002;5875-5885
46. Tabara H., Yigit E., Siomi H., Mello C.C. The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExH-box helicase to direct RNAi in C. elegans. Cell. 109:2002;861-871
47. Tijsterman M., Ketting R.F., Okihara K.L., Sijen T., Plasterk R.H. RNA helicase MUT-14-dependent gene silencing triggered in C. elegans by short antisense RNAs. Science. 295:2002;694-697
48. Kennerdell J.R., Yamaguchi S., Carthew R.W. RNAi is activated during Drosophila oocyte maturation in a manner dependent on aubergine and spindle-E. Genes Dev. 16:2002;1884-1889
49. Aravin A.A., Naumova N.M., Tulin A.V., Vagin V.V., Rozovsky Y.M., Gvozdev V.A. Double-stranded RNA-mediated silencing of genomic tandem repeats and transposable elements in the D. melanogaster germline. Curr Biol. 11:2001;1017-1027
50. Stapleton W., Das S., McKee B.D. A role of the Drosophila homeless gene in repression of Stellate in male meiosis. Chromosoma. 110:2001;228-240
51. Pal-Bhadra M., Leibovitch B.A., Gandhi S.G., Rao M., Bhadra U., Birchler J.A., Elgin S.C. Heterochromatic silencing and HP1 localization in Drosophilaare dependent on the RNAi machinery. Science. 303:2004;669-672
52. Himber C., Dunoyer P., Moissiard G., Ritzenthaler C., Voinnet O. Transitivity-dependent and -independent cell-to-cell movement of RNA silencing. EMBO J. 22:2003;4523-4533
53. Schwer B. A new twist on RNA helicases: DExH/D box proteins as RNPases. Nat Struct Biol. 8:2001;113-116
54. Carmell M.A., Xuan Z., Zhang M.Q., Hannon G.J. The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Genes Dev. 16:2002;2733-2742
55. •].
56. •].
57. •] describe the structure of the PAZ domain of Argonaute proteins, implicating this domain in nucleic acid binding. The weak affinity of the domain for nucleic acids suggests that the PAZ may be involved in transient interactions, perhaps as a molecular sensor for dsRNA end structures. These works gave the first indication of the molecular function of Argonaute proteins, a family of proteins universally required for RNAi.
58. Liu Q., Rand T.A., Kalidas S., Du F., Kim H.E., Smith D.P., Wang X. R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway. Science. 301:2003;1921-1925 The authors purify the siRNA-generating activity in Drosophila S2 cells and find it consists of a complex of Dicer2 and a dsRNA-binding domain protein called R2D2, a homolog of the C. elegans gene RDE-4. R2D2 is required for enhancement of siRNA incorporation into RISC. This work not only defined a new conserved activity in the RNAi pathway, but also dissected the mechanism of the key intersection between the generation of siRNAs and RISC assembly.
59. Tomari Y., Du T., Haley B., Schwarz D.S., Bennett R., Cook H.A., Koppetsch B.S., Theurkauf W.E., Zamore P.D. RISC assembly defects in the Drosophila RNAi mutant armitage. Cell. 116:2004;831-841
60. Schwarz D.S., Hutvagner G., Du T., Xu Z., Aronin N., Zamore P.D. Asymmetry in the assembly of the RNAi enzyme complex. Cell. 115:2003;199-208 The authors define a set of rules governing miRNA stability and RISC incorporation. This study has enabled the development of a new generation of short hairpin RNAs and siRNAs for use as tools for gene knock-down experiments.
61. Tahbaz N., Kolb F.A., Zhang H., Jaronczyk K., Filipowicz W., Hobman T.C. Characterization of the interactions between mammalian PAZ PIWI domain proteins and Dicer. EMBO Rep. 5:2004;189-194 The authors describe an interaction between the PIWI domain of Argonaute proteins and the RNaseIII domain/dsRNA-binding motif region of Dicer. Surprisingly, the interaction was found to inhibit Dicer cleavage. This is the first study to suggest a functional role for the PIWI domain.
62. Doi N., Zenno S., Ueda R., Ohki-Hamazaki H., Ui-Tei K., Saigo K. Short-interfering-RNA-mediated gene silencing in mammalian cells requires Dicer and eIF2C translation initiation factors. Curr Biol. 13:2003;41-46
63. Caudy A.A., Myers M., Hannon G.J., Hammond S.M. Fragile-X-related protein and VIG associate with the RNA interference machinery. Genes Dev. 16:2002;2491-2496
64. Caudy A.A., Ketting R.F., Hammond S.M., Denli A.M., Bathoorn A.M., Tops B.B., Silva J.M., Myers M.M., Hannon G.J., Plasterk R.H. A micrococcal nuclease homologue in RNAi effector complexes. Nature. 425:2003;411-414 This study identifies TSN-1, a conserved potential endonuclease, as a component of RISC complexes from a variety of organisms. Additionally, the authors show that the RISC purified from Drosophila S2 cells is largely conserved in other animals.
65. Hammond S.M., Boettcher S., Caudy A.A., Kobayashi R., Hannon G.J. Argonaute2, a link between genetic and biochemical analyses of RNAi. Science. 293:2001;1146-1150
66. Jin P., Zarnescu D.C., Ceman S., Nakamoto M., Mowrey J., Jongens T.A., Nelson D.L., Moses K., Warren S.T. Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nat Neurosci. 7:2004;113-117 This study supports a possible functional involvement of the RNAi machinery and miRNAs in neural development and fragile X mental retardation syndrome. The authors show that flies heterozygous for both Ago1 and fragile X mental retardation protein (dFMR1) show a neurogenesis defect just as severe as that seen in dFMR1 nulls, demonstrating that Ago1 is a critical limiting factor for dFMR1 function.
67. Nelson P.T., Hatzigeorgiou A.G., Mourelatos Z. miRNP:mRNA association in polyribosomes in a human neuronal cell line. RNA. 10:2004;387-394
68. Kim J., Krichevsky A., Grad Y., Hayes G.D., Kosik K.S., Church G.M., Ruvkun G. Identification of many microRNAs that copurify with polyribosomes in mammalian neurons. Proc Natl Acad Sci U S A. 101:2004;360-365
69. Verdel A., Jia S., Gerber S., Sugiyama T., Gygi S., Grewal S.I., Moazed D. RNAi-mediated targeting of heterochromatin by the RITS complex. Science. 303:2004;672-676 This paper describes he first biochemical connection between RNAi and the chromatin-modifying machinery. The authors find a complex in S. pombe containing Ago1, Chp1 and siRNAs.
70. Lehnertz B., Ueda Y., Derijck A.A., Braunschweig U., Perez-Burgos L., Kubicek S., Chen T., Li E., Jenuwein T., Peters A.H. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol. 13:2003;1192-1200
71. Rudert F., Bronner S., Garnier J.M., Dolle P. Transcripts from opposite strands of gamma satellite DNA are differentially expressed during mouse development. Mamm Genome. 6:1995;76-83
72. Lagos-Quintana M., Rauhut R., Meyer J., Borkhardt A., Tuschl T. New microRNAs from mouse and human. RNA. 9:2003;175-179
73. Hutvagner G., Zamore P.D. A microRNA in a multiple-turnover RNAi enzyme complex. Science. 297:2002;2056-2060
74. Martinez J., Patkaniowska A., Urlaub H., Luhrmann R., Tuschl T. Single-stranded antisense siRNAs guide target RNA cleavage in RNAi. Cell. 110:2002;563-574
75. Kennedy S., Wang D., Ruvkun G. A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans. Nature. 427:2004;645-649 A novel player in the RNAi machinery in C. elegans is described: a proposed 'siRNase', ERI-1, produces an enhanced RNAi phenotype when mutated. C. elegans naturally has a suppressed RNAi response in neurons, and this correlates with ERI-1 expression.
76. Feinberg E.H., Hunter C.P. Transport of dsRNA into cells by the transmembrane protein SID-1. Science. 301:2003;1545-1547 This study characterizes the properties of the C. elegans dsRNA transporter SID-1. Long dsRNA is taken up by SID-1 more efficiently than short dsRNA, and SID-1 transport of dsRNA does not require ATP. This is the first dsRNA transporter to be described and is implicated in intercellular dsRNA trafficking during a systemic RNAi response in C. elegans.
77. Juarez M.T., Kui J.S., Thomas J., Heller B.A., Timmermans M.C. microRNA-mediated repression of rolled leaf1 specifies maize leaf polarity. Nature. 428:2004;84-88 This study implicates a miRNA in regulation of maize leaf patterning, and presents compelling evidence that miRNA acts as a moveable signal.