Alan Frankel, PhD

About

Alan Frankel's lab focuses on RNA-protein recognition and the assembly of RNA-based regulatory complexes. His group uses 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, his 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.   Dr. Frankel co-leads the Tat and Rev projects on HARC. 

 

Lab website

Publications

  1. Faust TB, Li Y, Bacon CW, Jang GM, Weiss A, Jayaraman B, Newton BW, Krogan NJ, D'Orso I, Frankel AD. The HIV-1 Tat protein recruits a ubiquitin ligase to reorganize the 7SK snRNP for transcriptional activation. Elife. 2018 May 30; 7.
  2. Faust TB, Binning JM, Gross JD, Frankel AD. Making Sense of Multifunctional Proteins: Human Immunodeficiency Virus Type 1 Accessory and Regulatory Proteins and Connections to Transcription. Annu Rev Virol. 2017 Sep 29; 4(1):241-260.
  3. Nakamura RL, Burlingame MA, Yang S, Crosby DC, Talbot DJ, Chui K, Frankel AD, Renslo AR. Identification and Optimization of Thienopyridine Carboxamides as Inhibitors of HIV Regulatory Complexes. Antimicrob Agents Chemother. 2017 07; 61(7).
  4. Faust TB, Li Y, Jang GM, Johnson JR, Yang S, Weiss A, Krogan NJ, Frankel AD. PJA2 ubiquitinates the HIV-1 Tat protein with atypical chain linkages to activate viral transcription. Sci Rep. 2017 Mar 27; 7:45394.
  5. Fernandes JD, Faust TB, Strauli NB, Smith C, Crosby DC, Nakamura RL, Hernandez RD, Frankel AD. Functional Segregation of Overlapping Genes in HIV. Cell. 2016 Dec 15; 167(7):1762-1773.e12.
  6. Jayaraman B, Smith AM, Fernandes JD, Frankel AD. Oligomeric viral proteins: small in size, large in presence. Crit Rev Biochem Mol Biol. 2016 Sep; 51(5):379-394.
  7. Fernandes JD, Booth DS, Frankel AD. A structurally plastic ribonucleoprotein complex mediates post-transcriptional gene regulation in HIV-1. Wiley Interdiscip Rev RNA. 2016 07; 7(4):470-86.
  8. Jayaraman B, Mavor D, Gross JD, Frankel AD. Thermodynamics of Rev-RNA interactions in HIV-1 Rev-RRE assembly. Biochemistry. 2015 Oct 27; 54(42):6545-54.
  9. Dunyak BM, Nakamura RL, Frankel AD, Gestwicki JE. Selective Targeting of Cells via Bispecific Molecules That Exploit Coexpression of Two Intracellular Proteins. ACS Chem Biol. 2015 Nov 20; 10(11):2441-7.
  10. Jayaraman B, Crosby DC, Homer C, Ribeiro I, Mavor D, Frankel AD. RNA-directed remodeling of the HIV-1 protein Rev orchestrates assembly of the Rev-Rev response element complex. Elife. 2014 Dec 08; 3:e04120.
  11. Booth DS, Cheng Y, Frankel AD. The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA. Elife. 2014 Dec 08; 3:e04121.
  12. Nakamura RL, Landt SG, Mai E, Nejim J, Chen L, Frankel AD. A cell-based method for screening RNA-protein interactions: identification of constitutive transport element-interacting proteins. PLoS One. 2012; 7(10):e48194.
  13. D'Orso I, Jang GM, Pastuszak AW, Faust TB, Quezada E, Booth DS, Frankel AD. Transition step during assembly of HIV Tat:P-TEFb transcription complexes and transfer to TAR RNA. Mol Cell Biol. 2012 Dec; 32(23):4780-93.
  14. Faust T, Frankel A, D'Orso I. Transcription control by long non-coding RNAs. Transcription. 2012 Mar-Apr; 3(2):78-86.
  15. Fernandes J, Jayaraman B, Frankel A. The HIV-1 Rev response element: an RNA scaffold that directs the cooperative assembly of a homo-oligomeric ribonucleoprotein complex. RNA Biol. 2012 Jan; 9(1):6-11.
  16. 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. Global landscape of HIV-human protein complexes. Nature. 2011 Dec 21; 481(7381):365-70.
  17. Fahey ME, Bennett MJ, Mahon C, Jäger S, Pache L, Kumar D, Shapiro A, Rao K, Chanda SK, Craik CS, Frankel AD, Krogan NJ. GPS-Prot: a web-based visualization platform for integrating host-pathogen interaction data. BMC Bioinformatics. 2011 Jul 22; 12:298.
  18. Wang H, Ma X, Yeh YS, Zhu Y, Daugherty MD, Frankel AD, Musier-Forsyth K, Barbara PF. 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.
  19. Pastuszak AW, Joachimiak MP, Blanchette M, Rio DC, Brenner SE, Frankel AD. An SF1 affinity model to identify branch point sequences in human introns. Nucleic Acids Res. 2011 Mar; 39(6):2344-56.
  20. Daugherty MD, Liu B, Frankel AD. Structural basis for cooperative RNA binding and export complex assembly by HIV Rev. Nat Struct Mol Biol. 2010 Nov; 17(11):1337-42.
  21. D'Orso I, Frankel AD. HIV-1 Tat: Its Dependence on Host Factors is Crystal Clear. Viruses. 2010 Oct 01; 2(10):2226-2234.
  22. 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. Purification and characterization of HIV-human protein complexes. Methods. 2011 Jan; 53(1):13-9.
  23. Daugherty MD, Booth DS, Jayaraman B, Cheng Y, Frankel AD. 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.
  24. D'Orso I, Frankel AD. RNA-mediated displacement of an inhibitory snRNP complex activates transcription elongation. Nat Struct Mol Biol. 2010 Jul; 17(7):815-21.
  25. 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 JA, Chanda SK. Host cell factors in HIV replication: meta-analysis of genome-wide studies. PLoS Pathog. 2009 May; 5(5):e1000437.
  26. D'Orso I, Frankel AD. Tat acetylation modulates assembly of a viral-host RNA-protein transcription complex. Proc Natl Acad Sci U S A. 2009 Mar 03; 106(9):3101-6.
  27. Daugherty MD, D'Orso I, Frankel AD. A solution to limited genomic capacity: using adaptable binding surfaces to assemble the functional HIV Rev oligomer on RNA. Mol Cell. 2008 Sep 26; 31(6):824-34.
  28. D'Orso I, Grunwell JR, Nakamura RL, Das C, Frankel AD. Targeting tat inhibitors in the assembly of human immunodeficiency virus type 1 transcription complexes. J Virol. 2008 Oct; 82(19):9492-504.
  29. Mokdad A, Frankel AD. ISFOLD: structure prediction of base pairs in non-helical RNA motifs from isostericity signatures in their sequence alignments. J Biomol Struct Dyn. 2008 Apr; 25(5):467-72.
  30. Mills NL, Daugherty MD, Frankel AD, Guy RK. An alpha-helical peptidomimetic inhibitor of the HIV-1 Rev-RRE interaction. J Am Chem Soc. 2006 Mar 22; 128(11):3496-7.
  31. Landt SG, Ramirez A, Daugherty MD, Frankel AD. A simple motif for protein recognition in DNA secondary structures. J Mol Biol. 2005 Sep 02; 351(5):982-94.
  32. Calabro V, Frankel AD. Viral RNA gymnastics. Nat Chem Biol. 2005 Jul; 1(2):67-8.
  33. Landt SG, Tipton AR, Frankel AD. Localized influence of 2'-hydroxyl groups and helix geometry on protein recognition in the RNA major groove. Biochemistry. 2005 May 03; 44(17):6547-58.
  34. Calabro V, Daugherty MD, Frankel AD. A single intermolecular contact mediates intramolecular stabilization of both RNA and protein. Proc Natl Acad Sci U S A. 2005 May 10; 102(19):6849-54.
  35. Xie B, Calabro V, Wainberg MA, Frankel AD. Selection of TAR RNA-binding chameleon peptides by using a retroviral replication system. J Virol. 2004 Feb; 78(3):1456-63.
  36. Cheng AC, Frankel AD. Ab initio interaction energies of hydrogen-bonded amino acid side chain[bond]nucleic acid base interactions. J Am Chem Soc. 2004 Jan 21; 126(2):434-5.
  37. Das C, Edgcomb SP, Peteranderl R, Chen L, Frankel AD. Evidence for conformational flexibility in the Tat-TAR recognition motif of cyclin T1. Virology. 2004 Jan 05; 318(1):306-17.
  38. Das C, Frankel AD. Sequence and structure space of RNA-binding peptides. Biopolymers. 2003 Sep; 70(1):80-5.
  39. Cheng AC, Chen WW, Fuhrmann CN, Frankel AD. Recognition of nucleic acid bases and base-pairs by hydrogen bonding to amino acid side-chains. J Mol Biol. 2003 Apr 04; 327(4):781-96.
  40. Walberer BJ, Cheng AC, Frankel AD. Structural diversity and isomorphism of hydrogen-bonded base interactions in nucleic acids. J Mol Biol. 2003 Apr 04; 327(4):767-80.
  41. Xie B, Wainberg MA, Frankel AD. Replication of human immunodeficiency viruses engineered with heterologous Tat-transactivation response element interactions. J Virol. 2003 Feb; 77(3):1984-91.
  42. Peled-Zehavi H, Horiya S, Das C, Harada K, Frankel AD. Selection of RRE RNA binding peptides using a kanamycin antitermination assay. RNA. 2003 Feb; 9(2):252-61.
  43. Cheng AC, Calabro V, Frankel AD. Design of RNA-binding proteins and ligands. Curr Opin Struct Biol. 2001 Aug; 11(4):478-84.
  44. Frankel AD, Young JA. HIV-1: fifteen proteins and an RNA. Annu Rev Biochem. 1998; 67:1-25.