Faculty
Richard Carthew
Professor
Biochemistry, Molecular Biology and Cell Biology
PhD MIT
Email: r-carthew@northwestern.edu
Phone: (847) 467-4891
Fax: (847) 467-1380
Room: Pancoe Rm 3-111
Research Interests
RNAi and Gene Regulation
RNA has traditionally been thought of as a molecule that imparts information, structure or catalytic activities. Recently, a new role for RNA was discovered; it also regulates gene expression. This role, known as RNAi, mediates widespread defense against transposable elements and viruses, and also serves to regulate the expression of cellular protein-coding genes. The RNAs that participate in this process are 21 to 23 nucleotide fragments that are processed from double-stranded precursor molecules. Once formed, these siRNAs and microRNAs associate with cellular proteins and guide those proteins to complementary nucleic acids (chromosomal DNA or mRNA transcripts) in the cell. The complexes then effect a repression of the target nucleic acid. In the case of chromosomal DNA, the RNA-protein complex initiates the packaging of DNA into heterochromatin. In the case of mRNA, the complex initiates the destruction of the transcript or blocks its translation into a protein product. Our group studies the mechanism and function of this process in the model system Drosophila melanogaster. We combine genetics and biochemistry in Drosophila to understand its mechanistic principles.
The impact of RNAi has profoundly touched the fields of development and cell biology, functional genomics, human disease, and drug therapy. This is particularly seen with the small non-coding RNAs called microRNAs. This remarkable class of RNAs constitute 1% of the genes in the human genome, and they repress the expression of protein-coding genes by attenuating protein synthesis. Although it is difficult to estimate the extent of microRNA regulation, from 4 - 20% of protein-coding genes might be directly controlled by microRNAs. We are interested in understanding how microRNAs specifically inhibit their target genes and the biological consequences of this regulation. To this end, we discovered that microRNAs stimulate adult stem cells to divide continuously. Another function of microRNAs is to promote the differentiation of photoreceptor neurons. Our goal is to decipher the rules of microRNA regulation regarding target and biological specificity in diverse tissues of the body. The combined effects of microRNAs may affect the expression of many human genes, and misregulation of microRNAs appears to underlie complex disease phenomena such as cancer susceptibility and progression.
Selected Publications
Lucchetta EM, Carthew RW, Ismagilov RF. The endo-siRNA pathway is essential for robust development of the Drosophila embryo. PLoS One. 2009 Oct 23;4(10):e7576.
Lee YS, Pressman S, Andress AP, Kim K, White JL, Cassidy JJ, Li X, Lubell K, Lim do H, Cho IS, Nakahara K, Preall JB, Bellare P, Sontheimer EJ, Carthew RW. Silencing by small RNAs is linked to endosomal trafficking. Nat Cell Biol. 2009 Sep;11(9):1150-6. Epub 2009 Aug 16.
Li X, Cassidy JJ, Reinke CA, Fischboeck S, Carthew RW. A microRNA imparts robustness against environmental fluctuation during development. Cell. 2009 Apr 17;137(2):273-82.
Carthew RW, Sontheimer EJ. Origins and Mechanisms of miRNAs and siRNAs. Cell. 2009 Feb 20;136(4):642-55. Review.
Reinke CA, Carthew RW. BMP signaling goes posttranscriptional in a microRNA sort of way. Dev Cell. 2008 Aug;15(2):174-5.
Hayashi T, Xu C, Carthew RW. Cell-type-specific transcription of prospero is controlled by combinatorial signaling in the Drosophila eye. Development. 2008 Aug;135(16):2787-96. Epub 2008 Jul 17.
Hilgenfeldt S, Erisken S, Carthew RW. Physical modeling of cell geometric order in an epithelial tissue. Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):907-11. Epub 2008 Jan 11.
Carthew RW. Pattern formation in the Drosophila eye. Curr Opin Genet Dev. 2007 Aug;17(4):309-13. Epub 2007 Jul 6. Review.
Marques JT, Carthew RW. A call to arms: coevolution of animal viruses and host innate immune responses. Trends Genet. 2007 Jul;23(7):359-64. Epub 2007 Apr 27. Review.
Kim K, Lee YS, Carthew RW. Conversion of pre-RISC to holo-RISC by Ago2 during assembly of RNAi complexes. RNA. 2007 Jan;13(1):22-9. Epub 2006 Nov 22.
Carthew RW. Molecular biology. A new RNA dimension to genome control. Science. 2006 Jul 21;313(5785):305-6. No abstract available.
View all publications by Richard Carthew listed in the National Library of Medicine (PubMed). (IBiS students in blue)