The Frankel Lab focuses on RNA-protein recognition and the assembly of RNA-based regulatory complexes. We use biochemistry, structural methods, proteomics, and virology to investigate two essential regulatory complexes in HIV: the viral Tat protein and its interactions with the host transcription machinery, and the viral Rev protein and its interactions with host nuclear export complexes. In concert with proteomic studies of HIV-human protein complexes, our studies have led to an understanding of how the virus has evolved adaptable protein interfaces to hijack these two host machines and establish a unique regulatory circuit that drives gene expression during the HIV life cycle.

Faust T, Frankel A, D'Orso I. (2012) Transcription control by long non-coding RNAs.Transcription. 2012 Mar 1;3(2). [Epub ahead of print] [Download][Online] Fernandes J, Jayaraman B, Frankel A. (2012) The HIV-1 rev response element: An RNA scaffold that directs the cooperative assembly of a homo-oligomeric ribonucleoprotein complex. RNA Biol. 2012 Jan 1;9(1). [Epub ahead of print] [Download][Online] Jäger S, Cimermancic P, Gulbahce N, Johnson JR, McGovern KE, Clarke SC, Shales M, Mercenne G, Pache L, Li K, Hernandez H, Jang GM, Roth SL, Akiva E, Marlett J, Stephens M, D'Orso I, Fernandes J, Fahey M, Mahon C, O'Donoghue AJ, Todorovic A, Morris JH, Maltby DA, Alber T, Cagney G, Bushman FD, Young JA, Chanda SK, Sundquist WI, Kortemme T, Hernandez RD, Craik CS, Burlingame A, Sali A, Frankel AD, Krogan NJ. (2011) Global landscape of HIV-human protein complexes. Nature. 2011 Dec 21;481(7381):365-70. doi: 10.1038/nature10719. [Download][Online] Fahey ME, Bennett MJ, Mahon C, Jäger S, Pache L, Kumar D, Shapiro A, Rao K, Chanda SK, Craik CS, Frankel AD, Krogan NJ.(2011)GPS-Prot: a web-based visualization platform for integrating host-pathogen interaction data. BMC Bioinformatics. 2011 Jul 22;12:298. [Download][Online] Jäger S, Gulbahce N, Cimermancic P, Kane J, He N, Chou S, D'Orso I, Fernandes J, Jang G, Frankel AD, Alber T, Zhou Q, Krogan NJ.(2010) Purification and characterization of HIV-human protein complexes. Methods. 2011 Jan;53(1):13-9. Epub 2010 Aug 12. Review. 2010 Jul 13;107(28):12481-6. Epub 2010 Jun 28. [Download][Online] Pastuszak AW, Joachimiak MP, Blanchette M, Rio DC, Brenner SE, Frankel AD.(2011) An SF1 affinity model to identify branch point sequences in human introns. Nucleic Acids Res. 2011 Mar;39(6):2344-56. Epub 2010 Nov 10 [Download][Online] D'Orso I, Frankel AD. (2010) HIV-1 Tat: Its Dependence on Host Factors is Crystal Clear.Viruses. 2010 Oct 1;2(10):2226-2234. [Download][Online] Wang H, Ma X, Yeh YS, Zhu Y, Daugherty MD, Frankel AD, Musier-Forsyth K, Barbara PF. (2010) Comparative analysis of RNA/protein dynamics for the arginine-rich-binding motif and zinc-finger-binding motif proteins encoded by HIV-1. Biophys J. 2010 Nov 17;99(10):3454-62. [Download][Online] Daugherty MD, Liu B, Frankel AD. (2010) Structural basis for cooperative RNA binding and export complex assembly by HIV Rev. Nat Struct Mol Biol. 2010 Nov;17(11):1337-42. Epub 2010 Oct 17. [Download][Online] Daugherty, MD. Booth, DS. Jayaraman, B. Cheng, Y. Frankel, AD. (2010) HIV Rev response element (RRE) directs assembly of the Rev homooligomer into discrete asymmetric complexes. Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12481-6. Epub 2010 Jun 28. [Download][Online] D'Orso, I. Frankel, AD. (2010) RNA-mediated displacement of an inhibitory snRNP complex activates transcription elongation. Nat Struct Mol Biol. 2010 Jul;17(7):815-21. Epub 2010 Jun 20. [Download][Online] D'Orso, I. and Frankel, A.D. (2009) Tat acetylation modulates assembly of a viral-host RNA-protein transcription complex. Proc. Natl. Acad. Sci. 106, 3101-6. [Download] [Online] Bushman, FD. Malani, N. Fernandes, J. D'Orso, I. Cagney, G. Diamond, TL. Zhou, H. Hazuda, DJ. Espeseth, AS. König, R. Bandyopadhyay, S. Ideker, T. Goff, SP. Krogan, NJ. Frankel, AD. Young, John AT. and Chanda, SK. (2009) Host Cell Factors in HIV Replication: Meta-Analysis of Genome-Wide Studies, PLoS Pathog. 5, e1000437. [Download][Online] Daugherty MD, D'Orso ID, Frankel AD. (2008) A Solution to Limited Genomic Capacity: Using Adaptable Binding Surfaces to Assemble the Functional HIV Rev Oligomer on RNA. Mol Cell. [Download][Online] D'Orso I, Grunwell JR, Nakamura RL, Das C, Frankel AD. (2008) Targeting tat inhibitors in the assembly of human immunodeficiency virus type 1 transcription complexes. J Virol. 82,9492-504. [Download][Online] A. Mokdad and A.D. Frankel. ISFOLD: Structure prediction of base pairs in non-helical RNA motifs from isostericity signatures in their sequence alignments. J Biomol Struct Dyn, 25, 467-72. [Download][Online]