We aim to understand mechanisms of human innate immunity, response to damage, and stress. In particular, we are interested in structural and cell biology of pathways mediated by dsRNA, other kinds of RNA, and by receptor proteins that recognize or process these RNA molecules.
Intracellular response to dsRNA
Double-stranded RNA or dsRNA is a major regulator of gene expression in all mammalian cells. A number of membrane-tethered, cytosolic and nuclear proteins serve as receptors that recognize dsRNA and control dsRNA response. Often, dsRNA response is linked to the production of interferons, pro-inflammatory cytokines and control of innate and adaptive immunity.
Broader roles of these programs in homeostasis, cell cycle, differentiation, senescence and aging are also emerging.
Other signaling RNA
One of the key programs activated by dsRNA in all mammalian cells involves cleavage of the intracellular RNA pool by a kinase family receptor, RNase L. We are interested in structural and cell biology of RNase L.
We are also interested in a sister protein of RNase L, Ire1. Ire1 controls the unfolded protein response (UPR) by splicing an intron from a transcription factor XBP1 mRNA -- without using the spliceosome. As we have shown recently, Ire1 and RNase L employ similar mechanisms for RNA recognition.
- X-ray crystallography
- Human/murine cell biology
- Systems biology
Some of our recent work includes studies of receptors (sensors) involved in stress and immune responses.
Burroughs Wellcome Fund Award (2014)
Sidney Kimmel Foundation Award (2014)
General Biology Research Award, 6th Annual Awards, BioMed Central (London, 2011)
UCSF Dean’s Postdoctoral Research Prize and Lecture (2010)
Jane Coffin Childs Postdoctoral Fellow (2007-2010)
Cancer Research Institute (CRI) Postdoctoral Fellowship (2007)
Burroughs Wellcome Graduate Fellow (2001-2003)
George Soros International Scholar (ISSEP, 1995)
Han, Y.; Donovan, J.; Rath, S.; Whitney, G.; Chitrakar, A.; Korennykh, A., "Structure of Human RNase L Reveals the Basis for Regulated RNA Decay in the IFN Response." Science 2014, 343 (6176), 1244-1248.
Donovan, J.; Dufner, M.; Korennykh, A., "Structural basis for cytosolic double-stranded RNA surveillance by human oligoadenylate synthetase." Proceedings of the National Academy of Sciences of the United States of America 2013, 110 (5), 1652-1657.
Han, Y.; Whitney, G.; Donovan, J.; Korennykh, A., "Innate Immune Messenger 2-5A Tethers Human RNase L into Active High-Order Complexes." Cell Reports 2012, 2 (4), 902-913.
Korennykh, A.; Walter, P., "Structural Basis of the Unfolded Protein Response." Annual Review of Cell and Developmental Biology, Vol 28 2012, 28, 251-277.
Korennykh, A. V.; Korostelev, A. A.; Egea, P. F.; Finer-Moore, J.; Stroud, R. M.; Zhang, C.; Shokat, K. M.; Walter, P., "Structural and functional basis for RNA cleavage by Ire1." Bmc Biology 2011, 9.
Korennykh, A. V.; Egea, P. F.; Korostelev, A. A.; Finer-Moore, J.; Stroud, R. M.; Zhang, C.; Shokat, K. M.; Walter, P., "Cofactor-mediated conformational control in the bifunctional kinase/RNase Ire1." Bmc Biology 2011, 9.
Plantinga, M. J.; Korennykh, A. V.; Piccirilli, J. A.; Correll, C. C., "The Ribotoxin Restrictocin Recognizes Its RNA Substrate by Selective Engagement of Active Site Residues." Biochemistry 2011, 50 (14), 3004-3013.
Rubio, C.; Pincus, D.; Korennykh, A.; Schuck, S.; El-Samad, H.; Walter, P., "Homeostatic adaptation to endoplasmic reticulum stress depends on Ire1 kinase activity." Journal of Cell Biology 2011, 193 (1), 171-184.
Aragon, T.; van Anken, E.; Pincus, D.; Serafimova, I. M.; Korennykh, A. V.; Rubio, C. A.; Walter, P., "Messenger RNA targeting to endoplasmic reticulum stress signalling sites." Nature 2009, 457 (7230), 736-U9.
Korennykh, A. V.; Egea, P. F.; Korostelev, A. A.; Finer-Moore, J.; Zhang, C.; Shokat, K. M.; Stroud, R. M.; Walter, P., "The unfolded protein response signals through high-order assembly of Ire1." Nature 2009, 457 (7230), 687-U2.
Plantinga, M. J.; Korennykh, A. V.; Piccirilli, J. A.; Correll, C. C., "Electrostatic interactions guide the active site face of a structure-specific. ribonuclease to its RNA substrate." Biochemistry 2008, 47 (34), 8912-8918.
Korennykh, A. V.; Correll, C. C.; Piccirilli, J. A., "Evidence for the importance of electrostatics in the function of two distinct families of ribosome inactivating toxins." Rna-a Publication of the Rna Society 2007, 13 (9), 1391-1396.
Korennykh, A. V.; Plantinga, M. J.; Correll, C. C.; Piccirilli, J. A., "Linkage between substrate recognition and catalysis during cleavage of sarcin/ricin loop RNA by restrictocin." Biochemistry 2007, 46 (44), 12744-12756.
Korennykh, A. V.; Piccirilli, J. A.; Correll, C. C., "The electrostatic character of the ribosomal surface enables extraordinarily rapid target location by ribotoxins." Nature Structural & Molecular Biology 2006, 13 (5), 436-443.