Brian Rymond

  • Linda and Jack Gill Professor of Biology
  • Biochemistry Biophysics and Structural Biology
  • Biology
  • Cell and Developmental Biology
  • Genetics and Genomics
  • Microbiology
335A TH Morgan Bldg.
(859) 257-5530
Research Interests:
Education

Ph.D. State Univ. of New York at Albany, 1984

Research

Eukaryotic genome complexity is enriched by embedded introns which expand the number of proteins produced by alternative splicing, provide unique environments to embed genes and regulatory elements, and create opportunities for new gene assembly through recombination and intron evolution. Such benefits come at a cost, however, as approximately 15% of human genetic disorders result from splicing errors associated with cis- (splicing substrate) mutations that alter gene-delimited splice patterns or trans- (spliceosome subunit) mutations that may impair general pre-mRNA splicing. A better understanding of spliceosome composition and the molecular basis of splice site selection will facilitate the diagnosis and, ultimately, the treatment or correction of splicing-related disorders. The contribution of spliceosome assembly to the mechanism of pre-mRNA splicing is the focus of our work.

Metazoan genes may contain dozens of intron/exon borders, some of which are used only in response to specific developmental or environmental cues. For many genes it is the stable recruitment of the U2 snRNP to the branchpoint region of the pre-mRNA that modulates splice site choice. Pre-mRNA branchpoint recognition is complex and even in the case unregulated transcripts, progresses through the sequential association of multiple splicing factors (e.g., SF1/BBP – U2AF65/Mud2p) and snRNPs (U1, U2, and U6).

While the basic pathway of spliceosome assembly is well conserved through evolution, Saccharomyces cerevisiae (henceforth yeast) lacks canonical SR splicing factor regulators found in metazoa and relies on more rigidly conserved pre-mRNA consensus elements to direct splice site choice. Yeast gene structure is also simpler, with few genes containing more than a single intron. Accordingly, yeast offers an excellent model to investigate the assembly and function of the basal splicing apparatus in the absence of complications resulting from complex gene organization and splicing. Currently, we using genetic and proteomic approaches to investigate the dynamics of pre-mRNA branchpoint selection in vitro and in living cells.   

PubMed Publications*: 
  • Rivera-Robles, MJ ;Medina-Velázquez, J ;Asencio-Torres, GM ;González-Crespo, S ;Rymond, BC ;Rodríguez-Medina, J ;Dharmawardhane, S "Targeting Cdc42 with the anticancer compound MBQ-167 inhibits cell polarity and growth in the budding yeast S. cerevisiae." Small GTPases (2018): 1-11. Details. Full text
  • Santiago, E ;Akamine, P ;Snider, J ;Wong, V ;Jessulat, M ;Deineko, V ;Gagarinova, A ;Aoki, H.;Minic, Z ;Phanse, S ;San Antonio, A ;Cubano, LA ;Rymond, BC ;Babu, M ;Stagljar, I ;Rodriguez-Medina, JR "Novel Interactome of Saccharomyces cerevisiae Myosin Type II Identified by a Modified Integrated Membrane Yeast Two-Hybrid (iMYTH) Screen." G3 (Bethesda, Md.) 6, 5 (2016): 1469-74. Details. Full text
  • Banerjee, D ;McDaniel, PM ;Rymond, BC "Limited portability of G-patch domains in regulators of the Prp43 RNA helicase required for pre-mRNA splicing and ribosomal RNA maturation in Saccharomyces cerevisiae." Genetics 200, 1 (2015): 135-47. Details. Full text
  • Rymond, BC "The branchpoint binding protein: in and out of the spliceosome cycle." Advances in experimental medicine and biology 693, (2010): 123-41. Details.
  • Pandit, S.;Paul, S.;Zhang, L.;Chen, M.;Durbin, N.;Harrison, SM ;Rymond, BC "Spp382p interacts with multiple yeast splicing factors, including possible regulators of Prp43 DExD/H-Box protein function." Genetics 183, 1 (2009): 195-206. Details. Full text
  • Wang, Q.;Zhang, L.;Lynn, B.;Rymond, BC "A BBP-Mud2p heterodimer mediates branchpoint recognition and influences splicing substrate abundance in budding yeast." Nucleic acids research 36, 8 (2008): 2787-98. Details. Full text
  • Rymond, B. "Targeting the spliceosome." Nature chemical biology 3, 9 (2007): 533-5. Details. Full text
  • Pandit, S.;Lynn, B.;Rymond, BC "Inhibition of a spliceosome turnover pathway suppresses splicing defects." Proceedings of the National Academy of Sciences of the United States of America 103, 37 (2006): 13700-5. Details. Full text
  • Wang, Q.;He, J.;Lynn, B.;Rymond, BC "Interactions of the yeast SF3b splicing factor." Molecular and cellular biology 25, 24 (2005): 10745-54. Details. Full text
  • Dembla-Rajpal, N.;Seipelt, R.;Wang, Q.;Rymond, BC "Proteasome inhibition alters the transcription of multiple yeast genes." Biochimica et biophysica acta 1680, 1 (2004): 34-45. Details. Full text
  • Wang, Q.;Rymond, BC "Rds3p is required for stable U2 snRNP recruitment to the splicing apparatus." Molecular and cellular biology 23, 20 (2003): 7339-49. Details. Full text
  • Wang, Q.;Hobbs, K.;Lynn, B.;Rymond, BC "The Clf1p splicing factor promotes spliceosome assembly through N-terminal tetratricopeptide repeat contacts." The Journal of biological chemistry 278, 10 (2003): 7875-83. Details. Full text
  • Vincent, K.;Wang, Q.;Jay, S.;Hobbs, K.;Rymond, BC "Genetic interactions with CLF1 identify additional pre-mRNA splicing factors and a link between activators of yeast vesicular transport and splicing." Genetics 164, 3 (2003): 895-907. Details. Full text
  • Lybarger, S.;Beickman, K.;Brown, V.;Dembla-Rajpal, N.;Morey, K.;Seipelt, R.;Rymond, BC "Elevated levels of a U4/U6.U5 snRNP-associated protein, Spp381p, rescue a mutant defective in spliceosome maturation." Molecular and cellular biology 19, 1 (1999): 577-84. Details. Full text
  • Seipelt, RL ;Zheng, B.;Asuru, A.;Rymond, BC "U1 snRNA is cleaved by RNase III and processed through an Sm site-dependent pathway." Nucleic acids research 27, 2 (1999): 587-95. Details.
  • Chung, S.;McLean, MR ;Rymond, BC "Yeast ortholog of the Drosophila crooked neck protein promotes spliceosome assembly through stable U4/U6.U5 snRNP addition." RNA (New York, N.Y.) 5, 8 (1999): 1042-54. Details. Full text
  • McLean, MR ;Rymond, BC "Yeast pre-mRNA splicing requires a pair of U1 snRNP-associated tetratricopeptide repeat proteins." Molecular and cellular biology 18, 1 (1998): 353-60. Details. Full text
  • Xie, J.;Beickman, K.;Otte, E.;Rymond, BC "Progression through the spliceosome cycle requires Prp38p function for U4/U6 snRNA dissociation." The EMBO journal 17, 10 (1998): 2938-46. Details. Full text
  • Roy, J.;Zheng, B.;Rymond, BC ;Woolford JL, Jr "Structurally related but functionally distinct yeast Sm D core small nuclear ribonucleoprotein particle proteins." Molecular and cellular biology 15, 1 (1995): 445-55. Details. Full text
  • Lockhart, SR ;Rymond, BC "Commitment of yeast pre-mRNA to the splicing pathway requires a novel U1 small nuclear ribonucleoprotein polypeptide, Prp39p." Molecular and cellular biology 14, 6 (1994): 3623-33. Details. Full text
  • Rodriguez-Medina, JR ;Rymond, BC "Prevalence and distribution of introns in non-ribosomal protein genes of yeast." Molecular & general genetics : MGG 243, 5 (1994): 532-9. Details.
  • Rymond, BC "Convergent transcripts of the yeast PRP38-SMD1 locus encode two essential splicing factors, including the D1 core polypeptide of small nuclear ribonucleoprotein particles." Proceedings of the National Academy of Sciences of the United States of America 90, 3 (1993): 848-52. Details. Full text
  • Rymond, BC ;Rokeach, LA ;Hoch, SO "Human snRNP polypeptide D1 promotes pre-mRNA splicing in yeast and defines nonessential yeast Smd1p sequences." Nucleic acids research 21, 15 (1993): 3501-5. Details.
  • Blanton, S.;Srinivasan, A.;Rymond, BC "PRP38 encodes a yeast protein required for pre-mRNA splicing and maintenance of stable U6 small nuclear RNA levels." Molecular and cellular biology 12, 9 (1992): 3939-47. Details. Full text
  • Rymond, BC "Identification of sites of pre-MRNA/spliceosome association." SAAS bulletin, biochemistry and biotechnology 4, (1991): 76-80. Details.
  • Rymond, BC "The branchpoint binding protein: in and out of the spliceosome cycle." Advances in experimental medicine and biology 693, (0): 123-41. Details.
* Publications are automatically pulled from pubmed.gov based on a user-specific query. Results may include incorrect citations. See: Tutorial on improving PubMed results.
Other Publications

Rymond, BC., Going my way?  A tale of enzyme recruitment and activation 2016, Atlas of Science,

Rymond, B.C. The use of Saccharomyces cerevisiae to study the mechanism of pre-mRNA splicing. 2012,  Alternative Pre-mRNA Splicing: Theory and Protocols, Wiley-Blackwell,  (Eds., Stefan Stamm, Chris Smith, Reinhard Luhrmann)

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