SPECIAL TOPICS IN MOLECULAR GENETICS 2004

Class meets Wednesdays, 4-5:30, in Ullmann 723

Schedule of Topics    

Emmons Section

October 6, 2004    

Topic: C. elegans lin‑4, the first miRNA gene

Reviews:

Bartel, D. P.  (2004)  MicroRNAs: Genomics, biogenesis, mechanism, and function.  Cell 116, 281-297.

Hodgkin, J.  (1989)  Early worms.  Genetics 121, 1-3.

Horvitz, H. R., and Sulston, J. E.  (1990)  “Joy of the worm”  Genetics 126, 287-292.

Novina, C. D., and Sharp, P. A.  The RNAi revolution.  Nature 430, 161-164.

Papers:

Ambros, V., and Horvitz, H. R.  (1984)  Heterochronic mutants of the nematode Caenorhabditis elegans.  Science 226, 409-416.

Chalfie, M., Horvitz, H. R., and Sulston, J. E.  (1981)  Mutations that lead to reiterations in the cell lineages of C. elegans.  Cell 24, 59-69.

Lee, R. C., Feinbaum, R. L., and Ambros, V.  (1993)  The C. elegans heterochronic gene lin‑4 encodes small RNAs with antisense complementarity to lin‑14.  Cell 75, 843-854.

Ruvkun, G., and Giusto, J.  (1989)   The Caenorhabditis elegans heterochronic gene lin‑14 encodes a nuclear protein that forms a temporal developmental switch.  Nature 338, 313-319.

Wightman, B., Ha, I., and Ruvkun, G.  (1993)  Posttranscriptional regulation of the heterochronic gene lin‑14 by lin‑4 mediates temporal pattern formation in C. elegans.  Cell 75, 855-862.

October 13, 2004    

Topic:  miRNA genes, prevalence and biological function

Review

Ambros, V.  (2004)  The functions of animal microRNAs.  Nature 431, 350-355.

miRNA genes are widespread and abundant

Lau, N. C., Lim, L. P., Weinstein, E. G., and Bartel, D. P.  (2001)  An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.  Science 294, 858-862.

Lagos-Quintana, M., Rauhut, R., Lendeckel, W., and Tuschl, T.  (2001)  Identification of novel genes coding for small expressed RNAs.  Science 294, 853-858.

Lee, R. C., and Ambros, V.  (2001)  An extensive class of small RNAs in Caenorhabditis elegans.  Science 294, 862-864.

Lim, L. P., Glasner, M. E., Yekta, S., Burge, C. B., and Bartel, D. P.  (2003)  Vertebrate microRNA genes.  Science 299, 1540.

Pasquinelli, A.E., Reinhart, B.J., Slack, F., Martindale, M.Q., Kuroda, M.I., Maller, B., Hayward, D.C., Ball, E.E., Degnan, B., Muller, P., Spring, J., Srinivasan, A., Fishman, M., Finnerty, J., Corbo, J., Levine, M., Leahy, P., Davidson, E., Ruvkun, G. (2000) Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA.  Nature 408, 86-89.

Reinhart, B. J., Slack, F. J., Basson, M., Pasquinelli, A. E., Bettinger, J. C., Rougvie, A. E., Horvitz, H. R., Ruvkun, G. B.  (2000)  The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans.  Nature 403, 901-906.

Some known examples of regulatory functions of specific miRNA genes

Brenneck, J., Hipfner, D. R., Stark, A., Russell, R. B., and Cohen, S. M.  (2003)  bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila.  Cell 113, 25-36.

Chang, S., Johnston, R. J., Frokjaer-Jensen, C., Lockery, S., and Hobert, O.  (2004)  MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode.  Nature 430, 785-789.

Johnston, R. J., and Hobert, O.  (2003)  A microRNA controlling left/right neuronal asymmetry in Caenorhabidits eletgans.  Nature 426, 845-849.

Yekta, S., Shih, I., and Bartel, D.P.  (2004)  MicroRNA-directed cleavage of HOXB8 mRNA.  Science 304, 594-596.

Xu, P., Vernooy, S. Y., Guo, M., and Hay, B. A.  (2003)  The Drosophila microRNA mir‑14 suppresses cell death and is required for normal fat metabolism.  Curr. Biol. 13, 790-795.

October 20, 2004:  Discovery of RNAi.    

Review

Mello, C. C., and Conte, D.,  (2004)  Revealing the world of RNA interference.  Nature 431, 338-342.

Research papers

Fire, A., Xu, S., Montgomery, M.K., Kostas, S.A., Driver, S.E., and Mello, C.C.  (1998)  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.  Nature 391, 806-811.

Montgomery, M.K., Xu, S., and Fire, A.  (1998)  RNA as a target of double-stranded RNA-mediated genetic interference in Caenorhabditis elegans.  PNAS 95, 15502-15507.

Tabara, H., Sarkissian, M., Kelly, W. G., Fleenor, J., Grishok, A., Timmons, L., Fire, A., and Mello, C. C.  (1999)  The rde‑1 gene, RNA interference, and transposon silencing in C. elegans.  Cell 99, 123-132.

Winston, W. M., Molodowitch, C., and Hunter, C. P.  (2002)  Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1.  Science 295, 2456-2459.

October 27, 2004:  Biochemical dissection of the RNAi pathway. 

Research papers

Bernstein, E., Caudy, A. A., Hammond, S. M., and Hannon, G. J.  (2001)  Role for a bidentate ribonuclease in the initiation step of RNA interference.  Nature 409, 295-296.

Hammond, S. M., Bernstein, E., Beach, D., and Hannon, G. J.  (2000)  An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells.  Nature 404, 293-296.

Liu, J., Carmell,k M. A., Rivas, F. V., Marsden, C. G., Thomson, J. M., Song, J., Hammond, S. M., Joshua-Tor, L., and Hannon, G. J.  (2004)  Argonaute2 is the catalytic engine of mammalian RNAi.  Science 305, 1437-1441.

Song, J., Smith, S. K., Hannon, G. J., and Joshua-Tor, L.  (2004)  Crystal structure of Argonaute and its implications for RISC slicer activity.  Science 305, 1434-1437.

Zamore, P. D., Tuschl, T., Sharp, P. A., and Bartel, D. P.  (2000)  RNAi: Double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21-23 nucleotide intervals.  Cell 101, 25-33.

Fifth Session (November 3, 2004):  Convergence of miRNA and RNAi pathways, RNAi as natural transposon defense

Reviews

Carmell, M. A., Xuan, Z., Zhang, M. Q., and Hannon, G. J.  (2002)  The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis.  Genes and Dev 16, 2733-2742.

Plasterk, R. H. A., Izsvák, Z., and Ivics, Z.  (1999)  Resident aliens, the Tc1/mariner superfamily of transposable elements.  Trends in Genetics 15, 326-332.

Vastenhouw, N. L., and Plasterk, R. H. A.  (2004)  RNAi protects the Caenorhabditis elegans germline against transposition.  Trends in Genetics  20, 314-319.

Research papers

Convergence of miRNA and RNAi pathways

Grishok, A., Pasquinelli, A. E., Conte, D., Li, N., Parrish, S., Ha, I. Baillie, D. L., Fire, A., Ruvkun, G., and Mello, C. C.  (2001)  Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing.  Cell 106, 23-34.

Huntvágner, G., and Zamore, P. D.  (2002)  A microRNA in a multiple-turnover RNAi enzyme complex.  Science 297, 2056-2060.

Ketting, R. F., Fischer, S. E. J., Bernstein, E., Sijen, T., Hannon, G. J., and Plasterk, R. H. A.  (2001)  Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans.  Genes and Dev 15, 2654-2659.

Tabara, H., Yigit, E., Siomi, H., and Mello, C. C.  (2002)  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, 861-871.

 Transposon defense

Emmons, S. W., Yesner, L., Ruan, K. and Katzenberg, D. (1983) Evidence for a transposon in Caenorhabditis elegans.  Cell 32, 55-65.

Emmons, S. W. and Yesner, L. (1984) High-frequency excision of transposable element Tcl in the nematode Caenorhabditis elegans is limited to somatic cells.  Cell 36, 599-605.

Sijen, T., and Plasterk, R. H. A.  (2003)  Transposon silencing in the Caenorhabditis elegans germ line by natural RNAi.  Nature 426, 310-314.

Sixth Session (November 10, 2004):  Transcriptional gene silencing by RNAi

Reviews

Baulcombe, D.  (2004)  RNA silencing in plants.  Nature 431, 356-363.

Lippman, Z., and Martienssen, R  (2004)  The role of RNA interference in heterochromatic silencing.  Nature 431, 364-370.

Research papers

Hamilton, A. J., and Baulcomb, D. C.  (1999)  A species of small antisense RNA in posttranscriptional gene silencing in plants.  Science 286, 950-952.

Kawasaki, H., and Taira, K.,  (2004)  Induction of DNA methylation and gene silencing by short interfering RNAs in human cells.  Nature 431, 211-217.

Schramke, V., and Allshire, R.  (2003)  Hairpin RNAs and retrotransposon LTRs effect RNAi and chromatin-based gene silencing.  Science 301, 1069-1074.

Verdel, A., Jia, S., Gerber, S., Sugiyama, T., Gygi, S., Grewal, S. I. S., and Moazed, D.  RNAi-mediated targeting of heterochromatin by the RITS complex.  Science 303, 672-676.

Volpe, T., Kidner, C., Hall, I., Teng, G., Grewal, S., and Martienssen, R.  (2002)  Heterochromatic silencing and histone H3 lysine 9 methylation are regulated by RNA interference.  Science 297, 1833-1837.