James C. Carrington, Ph.D.

President
Donald Danforth Plant Science Center
Adjunct Professor
Biology

Plant and Microbial Biosciences Program

  • 314-587-1201

  • 314-587-1964

  • 1137

  • jcarrington@danforthcenter.org

  • http://carringtonlab.org/

  • genomics, functional genomics, biogenesis, systems biology, silencing pathways, plant biology, molecular biology, bioinformatics, RNA pathways

  • Focus on the biogenesis, functions, and evolutionof small RNA-directed silencing pathways in multicellular eukaryotes

Research Abstract:

Research in the Carrington lab focuses on RNA-mediated regulation and silencing of genomes, genes, and viruses. This lab focuses on the biogenesis, functions, and evolution of small RNA-directed silencing pathways in multicellular eukaryotes.

Small RNA-based silencing serves a regulatory mechanism during growth and development and in response to stress. It also functions as a transposon and repeat silencing mechanism, and as an antiviral response in plants and some animals. The Carrington lab uses a combination of genetics, genomics, computation and other approaches to address fundamental mechanistic problems using model systems, such as Arabidopsis thaliana and Brachypodium distachyon, but it also seeks to develop tools and approaches that have practical relevance. This lab is committed to the development of quantitative methods for mapping and quantifying high-throughput sequencing (HTS)-derived small RNA data, and to making these data available to the public through accessible, useful databases.

Diversification and evolution of silencing pathways.
HTS studies in a variety of plants and other organisms have revealed the diversity of ancient and recently evolved miRNA genes, and vast arrays of siRNAs from long dsRNA. The systematic analysis of mutants with defects in miRNA and siRNA function revealed several distinct biogenesis pathways for each class, and target RNAs that are regulated by small RNA families. Distinct small RNA biogenesis and effector components are involved in transcriptional and posttranscriptional silencing systems in plants. We have explored biogenesis, effector and specificity mechanisms of miRNA, trans-acting siRNA (tasiRNA), antiviral siRNA, and other small RNA classes using Arabidopsis thaliana.

Functional specialization of Argonautes and amplification of silencing signals.
The Carrington lab is particularly interested in the effector proteins - Argonautes (AGOs) - through which small RNAs function, and mechanisms of silencing amplification through RNA-dependent RNA polymerases. Plants have expanded sets of AGO genes that encode functionally diverse proteins. In addition to using HTS platforms to identify, characterize and quantify classes of small RNAs, the lab has profiled small RNAs that are affected by biotic stress, that associate with distinct Argonaute proteins, and that are associated with various growth and development phenotypes. The lab also explores the nature of small RNA regulatory networks, including small RNA that move between cells and AGO-small RNA-target interactions.

Selected Publications:

Fischer SE, Montgomery TA, Zhang C, Fahlgren N, Breen PC, Hwang A, Sullivan CM, Carrington JC, Ruvkun G. The ERI-6/7 Helicase Acts at the First Stage of an siRNA Amplification Pathway That Targets Recent Gene Duplications. PLoS Genetics 2011 Nov;7(11):e1002369. Epub 2011 Nov 10.

Cumbie JS, Kimbrel JA, Di Y, Schafer DW, Wilhelm LJ, Fox SE, Sullivan CM, Curzon AD, Carrington JC, Mockler TC, Chang JH. GENE-Counter: A Computational Pipeline for the Analysis of RNA-Seq Data for Gene Expression Differences. PLoS One 2011;6(10):e25279. Epub 2011 Oct 6.

Hu TT, Pattyn P, Bakker EG, Cao J, Cheng JF, Clark RM, Fahlgren N, Fawcett JA, Grimwood J, Gundlach H, Haberer G, Hollister JD, Ossowski S, Ottilar RP, Salamov AA, Schneeberger K, Spannagl M, Wang X, Yang L, Nasrallah ME, Bergelson J, Carrington JC, Gaut BS, Schmutz J, Mayer KF, Van de Peer Y, Grigoriev IV, Nordborg M, Weigel D, Guo YL. The Arabidopsis lyrata genome sequence and the basis of rapid genome size change. Nature Genetics 2011 May;43(5):476-81. Epub 2011 Apr 10.

Cuperus JT, Fahlgren N and Carrington JC. Evolution and functional diversification of MIRNA genes. The Plant Cell 2011 Feb;23(2):431-42. Epub 2011 Feb 11.

Zhang C, Montgomery TA, Gabel HW, Fischer SE, Phillips CM, Fahlgren N, Sullivan CM, Carrington JC, Ruvkun G. mut-16 and other mutator class genes modulate 22G and 26G siRNA pathways in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U.S.A. 2011 Jan 25;108(4):1201-8. Epub 2011 Jan 18.

Greenberg MV, Ausin I, Chan SW, Cokus SJ, Cuperus JT, Feng S, Law JA, Chu C, Pellegrini M, Carrington JC, Jacobsen SE. Identification of genes required for de novo DNA methylation in Arabidopsis. Epigenetics 2011 Mar;6(3):344-54. Epub 2011 Mar 1.

Smith KM, Sancar G, Dekhang R, Sullivan CM, Li S, Tag AG, Sancar C, Bredeweg EL, Priest HD, McCormick RF, Thomas TL, Carrington JC, Stajich JE, Bell-Pedersen D, Brunner M, Freitag M. Transcription factors in light and circadian clock signaling networks revealed by genomewide mapping of direct targets for neurospora white collar complex. Eukaryotic Cell 2010 Oct;9(10):1549-56. Epub 2010 Jul 30.

Wei T, Zhang C, Hong J, Xiong R, Kasschau KD, Zhou X, Carrington JC, Wang A. Formation of complexes at plasmodesmata for potyvirus intercellular movement is mediated by the viral protein P3N-PIPO. PLoS Pathogens 2010 Jun 24;6(6):e1000962.

Wei T, Zhang C, Hong J, Xiong R, Kasschau KD, Zhou X, Carrington JC, Wang A. RTM3, which controls long-distance movement of potyviruses, is a member of a new plant gene family encoding a meprin and TRAF homology domain-containing protein. Plant Physiology 2010 Jun 24;6(6):e1000962.

Cuperus JT, Carbonell A, Fahlgren N, Garcia-Ruiz H, Burke RT, Takeda A, Sullivan CM, Gilbert SD, Montgomery TA, Carrington JC. Unique functionality of 22-nt miRNAs in triggering RDR6-dependent siRNA biogenesis from target transcripts in Arabidopsis. Nature Structural Molecular Biology 2010 Aug;17(8):997-1003. Epub 2010 Jun 18.

For more publications please visit http://carringtonlab.org/.

Last Updated: 12/28/2011 2:28:01 PM

Infection of Arabidopsis by Turnip mosaic virus (TuMV) induces a number of developmental defects in vegetative and reproductive organs. The Carrington lab found that these defects, many of which resemble those in miRNA-deficient dicer-like1 (dcl1) mutants, were due to the TuMV-encoded RNA-silencing suppressor, P1/HC-Pro.
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