Marlene Belfort

Marlene Belfort, PhD

Introns and inteins in biotechnology and infectious disease.

The World Within Reach
Marlene Belfort, PhD
Distinguished Professor

School of Public Health
Department: Biomedical Sciences

Member, National Academy of Sciences
LSRB 2061
View: Personal page



Ph.D., University of California Irvine

The Belfort Lab

Research Interests

Introns and inteins in biotechnology and infectious disease.



  • Qu G, Kaushal PS, Wang J, Shigematsu H, Piazza CL, Agrawal RK, Belfort M, Wang HW. Structure of a group II intron in complex with its reverse transcriptase. Nat Struct Mol Biol. (2016) 23, 549-557.
  • Belfort, M. A decades-long journey with mobile introns. RNA. (2105) 21, 567-568.
  • Novikova O, Smith D, Hahn I, Beauregard A, Belfort M. Interaction between conjugative and retrotransposable elements in horizontal gene transfer. PLoS Genet. (2014). 10 (12).
  • Qu G, Dong X, Piazza CL, Chalamcharla VR, Lutz S, Curcio MJ, and Belfort M. RNA–RNA interactions and pre-mRNA mislocalization as drivers of group II intron loss from nuclear genomes. Proc. Natl. Acad. Sci. USA. (2014). 111, 6612-7.
  • Gupta K, Contreras LM, Smith D, Qu G, Huang T, Spruce LA, Seeholzer SH, Belfort M, Van Duyne GD. Quaternary arrangement of an active, native group II intron ribonucleoprotein complex revealed by small-angle X-ray scattering. Nucleic Acids Res. (2014). 42, 5347-60.
  • Contreras, L.M., Huang, T., Piazza, CL, Smith, D., Qu, Guosheng, G., Gelderman, G., Potratz, J., Russell, R. and Belfort, M. Group II intron-ribosome association protects intron RNA from degradation. RNA (2013) 11, 1497-509.
  • Belfort M, Bonocora RP. Homing endonucleases: from genetic anomalies to programmable genomic clippers. Methods Mol Biol. 2014;1123:1-26.
  • Bonocora RP, Belfort M. Mapping homing endonuclease cleavage sites using in vitro generated protein. Methods Mol Biol. 2014;1123:55-67.
  • Edgell, D.R., Chalamcharla, V.R. and Belfort, M. Learning to live together: mutualism between self-splicing introns and host genomes. BMC Biology (2011) 9, 22.
  • Robbins, J.B., Smith, D and Belfort, M. Redox-responsive zinc-finger is fidelity switch in homing endonuclease, promoting intron promiscuity under oxidative stress. Current Biol. (2011) 21, 243-248.
  • Huang T., Shaikh, T., Gupta, K., Contreras-Martin, L., Grassucci, R.A., Van Duyne, G.D., Frank, J.and Belfort, M. The group II intron ribonucleoprotein precursor is a large, loosely packed structure. Nucleic Acids Res. (2011) 39, 2845-2854. Featured article (top 5%).
  • Chalamcharla, V.R., Curcio, M.J. and Belfort, M. Nuclear expression of a group II intron is consistent with spliceosomal intron ancestry. Genes Dev. (2010) 24, 827-836. (Faculty of 1000, FFa10)
  • Stoddard, B. and Belfort, M. Social networking between mobile introns and their host genes. Mol. Micro. (2010) 78, 1-4.
  • Edgell, D.R., Gibb, E.A., Shub, D.A. and Belfort, M. Mobile DNA elements in T-even phage. BMC Virology J. (2010) 7, 290-305.
  • Coros, C.J., Piazza, C. L., Chalamcharla, V.R., Smith, D. and Belfort, M. Global regulators orchestrate group II intron retromobility. Mol. Cell (2009) 34, 250-256. (Faculty of 1000, FFa8)
  • Belfort, M. Scientific serendipity initiates an intron odyssey. J. Biol. Chem. (2009) 284, 29997-30003.
  • Liu, Q.Q., Dansereau, J.T., Puttamadappa, S,S, Shekhtman, A., Derbyshire, V. and Belfort, M. Role of the interdomain linker in distance determination for remote cleavage by homing endonuclease I-TevI . J. Mol. Biol. (2008) 379, 1094-1106.
  • Beauregard, A., Curcio, M.J. and Belfort, M. The take and give between retrotransposable elements and their hosts. Annu. Rev. Genetics. (2008) 42, 587-617.
  • Coros, C.J., Piazza, C. L. , Chalamcharla, V.R. and Belfort, M. A mutant screen reveals RNase E as a silencer of group II intron retromobility in Escherichia coli. RNA (2008) 14, 2634-2644.
  • Robbins, J.B., Stapleton, M., Stanger, M.J., Smith, D., Dansereau, J.T., Derbyshire, V., and Belfort, M. Homing endonuclease I-TevIII: dimerization as a means to a double-strand break. Nucleic Acids Res. (2007) 35, 1589-1600.
  • Liu, Q.Q., Derbyshire, V., Belfort, M. and Edgell, D.R. Distance determination by GIY-YIG intron endonucleases: Discrimination between repression and cleavage functions. Nucleic Acids Res. (2006) 34, 1755-1764.
  • Slagter-Jäger, J.G., Allen, G.S., Smith, D., Hahn, I.A., Frank, J. and Belfort, M. Visualization of a group II intron in the 23S rRNA of a stable ribosome. Proc. Natl. Acad. Sci. USA. (2006) 103, 9838- 9843.
  • Beauregard, A., Chalamcharla, V.R., Piazza, C.L., Belfort, M. and Coros, C.J. Bipolar localization of the group II intron Ll.LtrB is maintained in Escherichia coli deficient in nucleoid condensation, chromosome partitioning and DNA replication. Mol. Micro. (2006) 62, 709-722.
  • Blocker, F.J.H., Mohr, G., Conlan, L.H., Qi, L., Belfort, M. and Lambowitz, A.M. Domain structure and three-dimensional model of a group II intron-encoded reverse transcriptase. RNA (2005) 11, 14-28.
  • Coros, C.J., Landthaler, M., Piazza, C.L., Beauregard, A., Esposito, D., Perutka, J., Lambowitz, A.M. and Belfort, M. Retrotransposition strategies of the Lactococcus lactis Ll.LtrB group II intron are dictated by host identity and cellular environment. Mol. Microbiol. (2005) 56, 509-524.
  • Smith, D., Zhong, J., Matsuura, M., Lambowitz, A. M. and Belfort, M. Recruitment of host functions suggests a repair pathway for late steps in group II intron retrohoming. Genes Dev. (2005) 19, 2477-2487.
  • Conlan, L. H., Stanger, M. J., Ichiyanagi, K. and Belfort, M. Localization, mobility and fidelity of retrotransposed group II introns in rRNA genes. Nucl. Acids Res. (2005) 33, 5262-5270.
  • Edgell, D.R., Derbyshire, V., Van Roey, P., LaBonne, S., Stanger, M.J., Li, Z., Boyd, T.M., Shub, D.A., and Belfort, M. Intron-encoded homing endonuclease I-TevI also functions as a transcriptional autorepressor. Nat. Struct. Mol. Biol. (2004) 11, 936-944.
  • Edgell, D.R., Stanger, M.J., and Belfort, M. Coincidence of cleavage sites of intron endonuclease I-TevI and critical sequences of the host thymidylate synthase gene. J. Mol. Biol. (2004) 343, 1231-1241.
  • Edgell, D.R., Stanger, M.J. and M. Belfort. Importance of a single base pair for discrimination between intron-containing and intronless alleles by endonuclease I-BmoI. Curr. Biol. (2003) 13, 973-978.
  • Ichiyanagi, K., Beauregard, A. and Belfort, M. A bacterial group II intron favors retrotransposition into plasmid targets. Proc. Natl. Acad. Sci. USA (2003) 100, 15742-15747.
  • Belfort, M. Two for the price of one: a bifunctional intron-encoded DNA endonuclease-RNA maturase. Genes Dev. (2003) 17, 2860-2863.


  • Novikova O., Jayachandran P., Kelley DS., Morton Z., Merwin S., Topilina NI., Belfort M. Intein Clustering Suggests Functional Importance in Different Domains of Life. Mol Biol Evol. (2016) 33 (3): 783-99.
  • Topilina N., Green CM, Jayachandran P, Kelley DS, Stanger MJ, Piazza CL, Nayak S, Belfort M. SufB intein of Mycobacterium tuberculosis as a sensor for oxidative and nitrosative stresses. Proc. Natl. Acad. Sci. USA (2015) 112 (33):10348-53.
  • Topilina N., Novikova O., Stanger M., Banavali N.K., and Belfort M. Post-translational environmental switch of RadA activity by extein-intein interactions in protein splicing. Nucleic Acids Res. (2015) 43 (13):6631-48.
  • Novikova O, Topilina N, and Belfort M. Enigmatic distribution, evolution and function of inteins. J Biol Chem. (2014). 289 (21), 14490-7.
  • Pearson, C.S., Belfort, G., Belfort, M. and Shekhtman, A. Backbone assignments of mini-RecA intein with short exteins and an active N-terminal catalytic cysteine. Biomolecular NMR Assignments (2014) 9 (2):235-8.
  • Sorci, M., Dassa, B., Liu, H., Anand, G., Dutta, A., Pietrokovki, S., Belfort, M. and Belfort, G. Oriented covalent immobilization of antibodies for measurement of intermolecular binding forces between zipper-like contact surfaces of split inteins. Analytical Chemistry (2013) 85, 6080-60-88.
  • Dearden, A., Callahan, B., Van Roey, P., Li, Z., Kumar, U., Belfort, M. and Nayak, S.K. A conserved threonine spring-loads precursor for intein splicing. Protein Science (2013) 22, 557-563.
  • Callahan, B., Stanger, M. and Belfort, M. A redox trap to augment the intein toolbox. Biotech. and Bioeng. (2013) 110, 1565-1573.
  • Shemella, P.T., Soga, I., Pereira, B., Belfort, G., Belfort, M. and Nayak, S.K. Electronic structure of neighboring extein sequence modulates intein C-terminal cleavage activity. Biophys. J. (2011) 100, 2217-2225.
  • Callahan, B.P., Topilina, N., Stanger, M.J, Van Roey, P and Belfort, M. Catalytically competent intein caught in a redox trap: Structure, function, evolution. Nature Struc. Mol. Biol. (2011) 18, 630-633.
  • Pereira, B., Shemella, P.T., Amitai, G., Belfort, G., Nayak, S.K. and Belfort, M. Spontaneous proton transfer to a conserved intein residue determines on-pathway protein splicing. J. Mol. Biol. (2010) 406, 430-442.
  • Du, Z., Liu, Y., Ban, D., Lopez, M.M., Belfort, M. and Wang, C. Backbone dynamics and global effects of an activating mutation in minimized Mtu RecA inteins. J. Mol. Biol. (2010) 400, 755-767.
  • Zhang, L., Zheng, Y., Callahan, B., Belfort, M. and Liu, Y. Cisplatin inhibits protein splicing suggesting inteins as therapeutic targets in mycobacteria. J. Biol. Chem. (2010) 286, 1277-1282. Highlighted in Nature Chemical Biology.
  • Amitai, G., Callahan, B.P., Stanger, M.J., Belfort, G. and Belfort, M. Modulation of intein activity by its neighboring extein substrates. Proc. Natl. Acad. Sci. USA (2009) 106, 11005-11010.
  • Du, Z., Shemella, P.T., Liu, Y., McCallum, S.A., Pereira, B., Nayak, S.K., Belfort, G., Belfort, M. and Wang, C. Highly conserved histidine plays a dual catalytic role in protein splicing: a pKa shift mechanism. J. Am. Chem. Soc. (2009) 131, 11581-11589.
  • Hiraga, K., Soga, I., Dansereau, J.T., Pereira, B., Derbyshire, V., Du, Z., Wang, C., Van Roey, P., Belfort, G. and Belfort, M. Selection and structure of hyperactive inteins: peripheral changes relayed to the catalytic center. J. Mol. Biol. (2009) 393, 1106-1117.
  • Du, Z., Liu, Y., Zheng, Y., McCallum, S., Dansereau, J., Derbyshire, V., Belfort, M., Belfort, G., Van Roey, P. and Wang, C. 1H, 13C, and 15N NMR assignments of an engineered intein based on Mycobacterium tuberculosis RecA. Biomol. NMR Assign (2008) 2, 111-113.
  • Van Roey, P., Pereira, B., Li, Zh., Hiraga, K., Belfort, M., and Derbyshire, V. Crystallographic and mutational studies of Mycobacterium tuberculosis recA mini-inteins suggest a pivotal role for a highly conserved aspartate residue. J. Mol. Biol. (2007) 367, 162-173.
  • Miao, J., Wu, W., Spielmann, T., Belfort, M., Derbyshire, V., and Belfort, G. Single-step affinity purification of toxic and non-toxic proteins on a fluidics platform. Lab on a Chip (2005) 5, 248-253.
  • Belfort, M. Back to basics: structure, function, evolution and application of homing endonucleases and inteins, in Homing Endonucleases and Inteins, Eds. Belfort, M., Derbyshire, V., Stoddard, B.L. and Wood, D.W., Springer-Verlag (2005) pp. 1-10.
  • Hiraga, K., Derbyshire, V., Dansereau, J. T., Van Roey, P. and Belfort, M. Minimization and stabilization of the Mycobacterium tuberculosis recA intein. J. Mol. Biol. (2005) 354, 916-926.