By: Jack Liao- HOSTOS- Lincoln Academy of Science Jingwei Zhang- H.S. for Dual Language and Asian Studies Gabriell Copeland- Eagle Academy For Young Men Mentor: Professor Thomas Brennen Facility: Bronx Community College

Function of RNAi Potential, Unsolved Problems and Future Research REFERENCE Discovery and Introduction of RNAi

What is DNA? Deoxyribonucleic acid (DNA) is a nucleic acid —usually in the form of a double helix— that contains the genetic instructions specifying the biological development of all cellular forms of life, and many viruses. DNA never leaves the Nucleus.

RNA Ribonucleic acid (RNA) is a single- stranded nucleic acid which is transcribed from the base sequence of DNA. Double-stranded RNA (or dsRNA) is RNA with two complementary strands which forms the genetic material of some viruses. It acts as a trigger to initiate the process of RNA interference and is present as an intermediate step in the formation of siRNAs (small interfering RNAs). dsRNA

An Unusual Experience with Unexpected Results In 1990, scientists in the US and the Netherlands experimented with petunia plants by introducing “Extra” genes coded for purple pigmentation to increase the color purple in the plants. But instead, a non-pigmented petunia was created. What happened?petunia

What is RNAi? RNA interference (RNAi) is a mechanism in molecular biology whereby the presence of certain fragments of double-stranded RNA (dsRNA) interferes with the expression of a particular gene which shares a homologous sequence with the dsRNA.

A Double-Stranded RNA of 200 or more bases is introduced into the cell. RNAi activates.

An RNase III enzyme called Dicer, chops the double- stranded RNA into small interfering RNAs (siRNAs) of 20 or so bases.

The siRNAs then are bound to the RNA-Induced Silencing Complexes (RISC) where the siRNAs are unwound.

Using RNAi, we’re be able to turn off genes by adding extra copies or similar genes to the cells. With this, the potentials are enormous: Cures for Cancer and AIDS may become available. Silencing of non-desired genes. Human-Control gene expressions.

Cancer Cancer often involves mutant genes that promote uncontrolled cell growth. In the last few years, researchers have silenced more than a dozen known cancer-causing genes with RNAi. With RNAi, Cancers are preventable and curable. HIV As soon as RNA interference was discovered in human cells, scientists began exploring how it could be recruited to battle HIV. By late 2002, Phillip Sharp and colleagues at MIT announced they could interrupt various steps in the HIV life cycle with RNAi molecules.

At the age of 78, Markey Russell was diagnosed with Macular Degeneration, a genetic disease contributing to the excessive growth of blood vessels which can burst and destroy her vision. In an effort to work with the RNAi mechanism, Doctors injected dsRNA into Russell’s eye, signaling grown of blood vessel, in terms, hoping the homozygous genes would be destroyed. The outcome is promising. Mrs.Russell can see more clearly now.

Challenges and Future Research Finding the function for each of the billion specific genes. Better understanding of the RNAi mechanism. Utilizing the absolute ability of RNAi. Discovering cures for illness using RNAi. Ways to deploy RNAi treatment …

General references Robert OlbyRobert Olby; "The Path to The Double Helix: Discovery of DNA"; first published in 0ctober 1974 by MacMillan, with foreword by Francis Crick; ISBN ; the definitive DNA textbook, revised in 1994, with a 9 page postscript.ISBN Ridley, MattRidley, Matt; Francis Crick: Discoverer of the Genetic Code (Eminent Lives) first published in June 2006 in the USA and then to be in the UK September 2006, by HarperCollins Publishers; 192 pp, ISBN XISBN X Watson, James D. and Francis H.C. Crick. A structure for Deoxyribose Nucleic Acid (PDF). Nature 171, 737 – 738, 25 April 1953.A structure for Deoxyribose Nucleic AcidNature25 April1953 Watson, James D. DNA: The Secret of Life ISBN ISBN Watson, James D. The Double Helix: A Personal Account of the Discovery of the Structure of DNA (Norton Critical Editions). ISBN The Double Helix: A Personal Account of the Discovery of the Structure of DNA (Norton Critical Editions)ISBN Chomet, S. (Ed.), DNA Genesis of a Discovery, Newman-Hemisphere Press, London, Delmonte, C.S. and Mann, L.R.B. Variety in DNA tertiary structure. Current Science, 85 (11), 1564 – 1570, 10 December 2003.Variety in DNA tertiary structure Miller, Kenneth R., and Levin, Joseph. Biology. Saddle River, New Jersey: Prentice Hall, ^ a b Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipurksy SL, Darnell J. (2004). Molecular Cell Biology 5th ed. WH Freeman: New York, NY.ab ^^ Schramke V, Allshire R. (2003). Hairpin RNAs and retrotransposon LTRs effect RNAi and chromatin-based gene silencing. Science 301(5636): PMID PMID ^^ Stram Y, Kuzntzova L. (2006). Inhibition of viruses by RNA interference. Virus Genes 32(3): ^^ Cerutti H, Casas-Mollano JA. (2006). On the origin and functions of RNA-mediated silencing: from protists to man. Curr Genet 50(2): ^^ Holmquist GP, Ashley T. (2006). Chromosome organization and chromatin modification: influence on genome function and evolution. Cytogenet Genome Res 114(2): ^^ Volpe TA, Kidner C, Hall IM, Teng G, Grewal SI, Martienssen RA. (2002). Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297(5588): PMID PMID ^^ Lee RC, Feinbaum RL, Ambros V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5): ^^ Palatnik JF, Allen E, Wu X, Schommer C, Schwab R, Carrington JC, Weigel D. (2003). Control of leaf morphogenesis by microRNAs. Nature 425(6955): ^^ Morita T, Mochizuki Y, Aiba H. (2006). Translational repression is sufficient for gene silencing by bacterial small noncoding RNAs in the absence of mRNA destruction. Proc Natl Acad Sci 103(13): ^^ Napoli C., Lemieux C., and Jorgensen R. (1990) "Introduction of a chalcone synthase gene into Petunia results in reversible co-suppression of homologous genes in trans". Plant Cell 2: ^^ Fire A., Xu S., Montgomery M.K., Kostas S.A., Driver S.E., Mello C.C. (1998). "Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans". Nature 391: Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans ^^ Dzitoyeva S, Dimitrijevic N, Manev H. (2003). Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence. Proc Natl Acad Sci 100(9): PMID PMID ^^ Fortunato A, Fraser AG. (2005). Uncover genetic interactions in Caenorhabditis elegans by RNA interference. Biosci Rep 25(5-6): PMID PMID PBS NOVA Science Now RNAi video, RNAi Explain, The RNA Cure, Ask the Expert( Aug 28th 2006) Available at (

Dr. Sat Bhattacharya Harlem Children Society Dr. Thomas Brennan Bronx Community College (Chemistry Department) BCC Office of Collaborative Program (College Now) City University of New York National Science Foundation Howard Hughes Medical Institute Biological Science Curriculum Study Pathways Bioinformatics & Biomolecular Center