Professor, Biological Chemistry, University of California Los Angeles
611 Charles E. Young Dr. E
Los Angeles, CA 90095
Office Phone Number:
Director, Biochemistry, Biophysics & Structural Biology GPB Home Area
Member, Gene Regulation GPB Home Area, JCCC Gene Regulation Program Area
My research group is interested to understand how non-coding RNAs function by forming defined three-dimensional structures and by interacting with proteins. In particular, we are investigating how a class of small RNAs (called microRNA or miRNA) is processed in human. The projects will be investigated using X-ray crystallography, biochemistry and in vitro evolution methods. MiRNAs are involved in many important biological functions, and are emerged as a new class of oncogenes and tumor suppressors. They regulate the expression of many protein-coding genes by targeting their messenger RNAs (mRNAs) for degradation or translational repression. To become the short mature functional forms, the long primary transcripts (pri-miRNAs) need to be specifically recognized and cleaved by a series of cellular processing factors. The first step of this processing pathway involves two protein factors, Drosha (a ribonuclease III family member) and DGCR8 (an RNA binding protein). We are characterizing the RNA binding and cleavage properties of these proteins, in the hope to use the knowledge to improve the algorithms to predict new miRNA genes and to design gene knockdown technologies by mimicking pri-miRNA. We recently found surprisingly that DGCR8 is a heme-binding protein and heme is likely involved in the regulation of miRNA processing. Our findings have important implications to the biological functions of miRNAs and heme, and to the pathogenesis and therapies of diseases such as cancers and Alzheimer’s disease.
Dr. Guo is a structural biologist and biochemist who joined the UCLA School of Medicine faculty in July 2004. He earned his B.S. in Biophysics at the Nankai University and M.S. in Physical Chemistry at the Peking University, both in China. Dr. Guo received his Ph.D. in Biochemistry and Biophysics at the University of Pennsylvania in 2000. In graduate school, he studied the Cre-loxP site-specific DNA recombination using X-ray crystallography. He was a postdoctoral fellow with Dr. Thomas Cech at the University of Colorado at Boulder, where he worked on the thermostability and crystal structure of large ribozymes. He has been on the faculty at UCLA since 2004. His ressearch group studies the molecular mechanism of RNA processing and develops therapeutics that target RNA.
A selected list of publications:
- Senturia, R., Laganowsky, A., Barr, I., Brooke D. Scheidemantle, B.D., and Guo, F. Dimerization and heme binding are conserved in amphibian and starfish homologues of the microRNA processing protein DGCR8 PLoS ONE, 2012; 7(7): e39688.
- Gong, M., Chen, Y., Senturia, R., Ulgherait, M., Faller, M., and Guo, F. Caspases cleave and inhibit the microRNA processing protein DiGeorge Critical Region 8. Protein Sci, 2012; 21: 797-808.
- Barr, I., Smith, A.T., Chen, Y., Senturia, R., Burstyn, J.N., and Guo, F. Ferric, not ferrous, heme activates RNA-binding protein DGCR8 for primary microRNA processing Proc. Natl. Acad. Sci. USA, 2012; 109: 1919-1924.
- Meer, E.J., Wang, D.O., Kim, S.M., Barr, I., Guo, F., and Martin, K.C. Identification of a cis-acting element that localizes mRNA to synapses, Proc. Natl. Acad. Sci. USA, 2012; 109: 4639-4644.
- Barr, I., Smith, A.T., Senturia, R., Chen, Y., Scheidemantle, B.D., Burstyn, J.N., and Guo, F. DiGeorge Critical Region 8 (DGCR8) is a double-cysteine-ligated heme protein J. Biol. Chem, 2011; 286: 16716-25.
- Faller, M., Toso, D., Matsunaga, M., Atanasov, I., Senturia, R., Chen, Y., Zhou, Z.H., and Guo, F. DGCR8 recognizes primary transcripts of microRNAs through highly cooperative binding and formation of higher-order structures RNA, 2010; 16: 1570-1583.
- Senturia, R., Faller, M., Yin, S., Loo, J.A., Cascio, D., Sawaya, M.R., Hwang, D., Clubb, R.T., and Guo, F. Structure of the dimerization domain of DiGeorge Critical Region 8 Protein Sci, 2010; 19: 1354-1365.
- Miallau Linda, Faller Michael, Chiang Janet, Arbing Mark, Guo Feng, Cascio Duilio, Eisenberg David Structure and proposed activity of a member of the VapBC family of toxin-antitoxin systems. VapBC-5 from Mycobacterium tuberculosis J, Biol. Chem, 2009; 284(1): 276-83.
- Wang, Q., Barr, I., Guo, F., Lee, C. Evidence of a novel RNA secondary structure in the coding region of HIV-1 pol gene RNA, 2008; 14(12): 2478-88.
- Faller Michael, Guo Feng MicroRNA biogenesis: there’s more than one way to skin a cat Biochim. Biophys. Acta, 2008; 1779(11): 663-7.
- Faller, M., Matsunaga, M., Yin, S., Loo, J., and Guo, F. Heme is involved in microRNA processing, Nat. Struct. Mol. Biol, 2007; 14(1): 23-29.
- Guo, F., Gooding, A.R. and Cech, T.R. Comparison of crystal structure interactions and thermodynamics for stabilizing mutations in the Tetrahymena ribozyme, RNA, 2006; 12: 387-395.
- Guo, F Gooding, AR Cech, TR Structure of the Tetrahymena ribozyme: base triple sandwich and metal ion at the active site Mol. Cell. , 2004; 16(3): 351-62.
- Guo, F Cech, TR Evolution of Tetrahymena ribozyme mutants with increased structural stability Nat. Struct. Biol. , 2002; 9(11): 855-61.
- Guo, F Cech, TR In vivo selection of better self-splicing introns in Escherichia coli: the role of the P1 extension helix of the Tetrahymena intron RNA, 2002; 8(5): 647-58.
- Guo, F Gopaul, DN Van Duyne, GD Asymmetric DNA bending in the Cre-loxP site-specific recombination synapse Proceedings of the National Academy of Sciences of the United States of America. , 1999; 96(13): 7143-8.
- Gopaul, DN Guo, F Van Duyne, GD Structure of the Holliday junction intermediate in Cre-loxP site-specific recombination EMBO J, 1998; 17(14): 4175-87.
- Guo, F., Gopaul, D.N., van Duyne, G.D. Structure of Cre recombinase complexed with DNA in a site-specific recombination synapse Nature, 1997; 389(6646): 40-6.
- Weitz, S. H., Gong, M., Barr, I., Weiss, S., and Guo, F. Processing of microRNA primary transcripts requires heme in mammalian cells Proc. Natl. Acad. Sci. USA, 2014; 111: 1861-1866.
- Quick-Cleveland, J., Jacob, J.P., Weitz, S.H., Shoffner, G., Senturia, R., and Guo, F. The DGCR8 RNA-binding heme domain recognizes primary microRNAs by clamping the hairpin Cell Rep, 2014; 7(6): 1994-2005.
- Chin, R.M., Fu, X., Pai, M.Y., Vergnes, L., Hwang, H., Deng, G., Diep, S., Lomenick, B., Meli, V.S., Monsalve, G.C., Hu, E., Whelan, S.A., Wang, J.X., Jung, G., Solis, G.M., Fazlollahi, F., Kaweeteerawat, C., Quach, A., Nili, M., Krall, A.S., Godwin, H.A., Chang, H.R., Faull, K.F., Guo, F., Jiang, M., Trauger, S.A., Saghatelian, A., Braas, D., Christofk, H.R., Clarke, C.F., Teitell, M.A., Petrascheck, M., Reue, K., Jung, M.E., Frand, A.R., and Huang, J. The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR Nature, 2014; 510: 397-410.
- Barr, I. and Guo, F. Primary microRNA processing assay reconstituted using recombinant Drosha and DGCR8 Methods Mol. Biol, 2014; 1095: 73-86.
- Januszyk Kurt, Fleissner Mark R, Atchabahian Lara, Shieh Fa-Kuen, Altenbach Christian, Martin Sandra L, Guo Feng, Hubbell Wayne L, Clubb Robert T Site-directed spin labeling electron paramagnetic resonance study of the ORF1 protein from a mouse L1 retrotransposon Protein Sci, 2011; 20(7): 1231-43.
- Lal Sneha, Comer Jonathan M, Konduri Purna C, Shah Ajit, Wang Tianyuan, Lewis Anthony, Shoffner Grant, Guo Feng, Zhang Li Heme promotes transcriptional and demethylase activities of Gis1, a member of the histone demethylase JMJD2/KDM4 family Nucleic Acids Res, 2018; 46(1): 215-228.
- Hines Judy P, Smith Aaron T, Jacob Jose P, Lukat-Rodgers Gudrun S, Barr Ian, Rodgers Kenton R, Guo Feng, Burstyn Judith N CO and NO bind to Fe(II) DiGeorge critical region 8 heme but do not restore primary microRNA processing activity J. Biol. Inorg. Chem, 2016; 21(8): 1021-1035.
- Barr Ian, Weitz Sara H, Atkin Talia, Hsu PeiKen, Karayiorgou Maria, Gogos Joseph A, Weiss Shimon, Guo Feng Cobalt(III) Protoporphyrin Activates the DGCR8 Protein and Can Compensate microRNA Processing Deficiency Chem. Biol, 2015; 22(6): 793-802.
- Shoffner Grant M, Wang Ruixuan, Podell Elaine, Cech Thomas R, Guo Feng In Crystallo Selection to Establish New RNA Crystal Contacts Structure, 2018; 26(9): 1275-1283.
- Tayeb-Fligelman Einav, Cheng Xinyi, Tai Christen, Bowler Jeannette T, Griner Sarah, Sawaya Michael R, Seidler Paul M, Jiang Yi Xiao, Lu Jiahui, Rosenberg Gregory M, Salwinski Lukasz, Abskharon Romany, Zee Chih-Te, Hou Ke, Li Yan, Boyer David R, Murray Kevin A, Falcon Genesis, Anderson Daniel H, Cascio Duilio, Saelices Lorena, Damoiseaux Robert, Guo Feng, Eisenberg David S Inhibition of amyloid formation of the Nucleoprotein of SARS-CoV-2 bioRxiv : the preprint server for biology, 2021; 21(1): 155.
- Shoffner, G.M., Peng, Z., and Guo, F. Structures of microRNA-precursor apical junctions and loops reveal non-canonical base pairs important for processing bioRxiv, 2020; .
- Weitz, S.H., Quick-Cleveland, J., Jacob, J.P., Barr, I., Senturia, R., Koyano, K., Xiao, X., Weiss, S., and Guo, F. Fe(III) heme sets an activation threshold for processing distinct groups of pri-miRNAs in mammalian cells bioRxiv, 2020; .