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.

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.

Wang XH, Aliyari R, Li WX, Li HW, Kim K, Carthew R, Atkinson P, Ding SW. RNA interference directs innate immunity against viruses in adult Drosophila. Science. 2006 Apr 21;312(5772):452-4. Epub 2006 Mar 23.

Carthew RW. Gene regulation by microRNAs. Curr Opin Genet Dev. 2006 Apr;16(2):203-8. Epub 2006 Feb 28. Review.

Bayraktar J, Zygmunt D, Carthew RW. Par-1 kinase establishes cell polarity and functions in Notch signaling in the Drosophila embryo. J Cell Sci. 2006 Feb 15;119(Pt 4):711-21.

Hatfield S.D., Shcherbata H.R., Fischer K.A., Nakahara K., Carthew R.W., and H. Ruohola-Baker. (2005) Stem cell division is regulated by the microRNA pathway. Nature 435, 974-978.

Sontheimer E.K., and R.W. Carthew (2005) Functional roles of endogenous miRNAs and siRNAs. Cell 122, 9-12.

Nakahara, K. and R.W. Carthew (2004) Expanding roles for miRNAs and siRNAs in cell regulation. Curr. Topics Cell Biol. 16, 127-133.

Lee Y.S., Nakahara K., Pham J.W., Kim K., He Z., Sontheimer E.J., and R.W. Carthew (2004) Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell 117, 69-81.

Pham J.W., Pellino J.L., Lee Y.S., Carthew R.W., and E.J. Sontheimer (2004) A Dicer-2-dependent 80S complex cleaves targeted mRNAs during RNAi in Drosophila. Cell 117, 83-94.

Hayashi T., and R.W. Carthew (2004) Surface mechanics mediate pattern formation in the developing retina. Nature 431, 647-652.

Carthew, R.W. (2003) RNAi Applications in Drosophila melanogaster. In: Gene Silencing. (ed. G. Hannon) Cold Spring Harbor Press, NY. pp 361-400.

Kennerdell, J.R., Yamaguchi, S. and R.W. Carthew (2002) RNAi is activated during Drosophila oocyte maturation in a manner dependent on aubergine and spindle-E. Genes Dev. 16, 1884-1889.

View all publications by publications by Richard Carthew listed in the National Library of Medicine (PubMed).