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Richard E. Davis, PhD

Associate Professor

Ph.D., The University of Massachusetts at Amherst

Contact Information:

Phone: (303) 724-3226
Fax: (303) 724-3215
E-mail: Richard.Davis@ucdenver.edu

Davis Lab Website

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Graduate Program Memberships

Molecular Biology​
Microbiology​
Biomedical Sciences
Structural Biology & Biophysics​
Cell Biology, Stem Cells and Development
MSTP


1. Spliced leader RNA trans-splicing in metazoa

Spliced leader (SL) RNA trans-splicing generates the mature 5’ ends of mRNAs by addition of a spliced leader sequence to the 5’ end of a pre-mRNA. Addition of the SL sequence also brings a new and an atypical cap to the RNA, a trimethylguanosine cap (m2,2,7GpppN) compared to the typical m7GpppN eukaryotic cap. Current studies involve analysis of

  • Functional significance of trans-splicing
  • Protein and mRNA metabolism adaptation to spliced leader trans-splicing
  • Post-transcriptional role of trans-splicing in mRNA translation and stability
  • Structure/function of mRNA cap-interacting proteins in trans-splicing and mRNA metabolism (eIF4E, eIF4G, nuclear cap binding complex, decapping, etc.)

2. Chromatin Diminution

Genome maintenance and stability are essential, and an organism’s genome rarely changes. But a few organisms undergo chromatin diminution, a programmed process that eliminates specific DNA sequences from the genome. In the parasitic nematode, Ascaris, 25% of the genome is eliminated in the somatic lineages during the 3rd through 5th cleavage (4 to 16 cell stage), while the germline genome remains intact. Both repetitive and unique sequences (genes) are lost during chromatin diminution. The elimination results in chromosome breakage and the loss of chromosome termini as well as the generation of new chromosomes. Studies are underway to compare the genome of the somatic cells which have undergone chromatin dimimution with the germline genome to determine

  • What is the mechanism of chromosome breakage?
  • Where are the chromosome breaks? What rearrangements occur?
  • How are the breakpoints and sequences eliminated defined?
  • What genes are lost?
  • What are the somatic consequences of DNA elimination?

3. Small RNA function and silencing in nematodes

A variety of small RNAs including endogenous siRNA (22G-RNAs and 26G-RNAs) and miRNAs play key roles in silencing in the Ascaris germline, gametogenesis, and early development. Current studies are addressing the role and function of these small RNAs with a particular focus on the mechanisms of small RNA silencing and biogenesis in novel cell-free systems.

  • Function and role of small RNAs in Ascaris development, gametogenesis, and the germ line
  • Mechanisms of small RNA silencing and biogenesis in Ascaris

4. Regulation of Ascaris mRNA metabolism during gametogenesis and early embryo development

Zygote maturation and early development in Ascaris are very slow compared to C. elegans and enables the staging of large amounts of material for developmental studies. This enables us to carry out analysis of post-transcriptional gene regulation including

  • Developmental mRNA analyses (RNA-seq analysis) combined with small RNA profiling
  • Translation and stability during early development (polysome RNA-seq analysis)
  • mRNA masking, P-bodies, and P-granules
​

Current Lab Colleagues

 Results From Research : Selected site and subsites
PicturesLast NameFirst NameJob TittleEmailBio Page
PiecykKarolinaVisiting ScientistKarolina.Piecyk@Ucdenver.edu  
RoyJuliannePostdoctoral FellowJulianne.Roy@Ucdenver.edu  
ThorneAliciaGraduate StudentAlicia.Thorne@UCDenver.edu  
WallaceAdamProfessional Research AssistantAdam.Wallace@UCDenver.edu  
WangJian BinPostdoctoral FellowJianbin.Wang@UCDenver.edu  


Wang, J., Czech, B. Crunk, A., Wallace, A., Mitreva, M., Hannon, G., and R.E. Davis. 2011. Deep small RNA sequencing from the nematode Ascaris reveals conservation, functional diversification, and novel developmental profiles. Genome Research 21:1462–1477. PDF, Supplementary Material, or Pubmed

Liu, W. ..............Jones, D., R.E. Davis. 2011. Structural Basis for Nematode eIF4E binding an m2,2,7G-Cap and its Implications for Translation Initiation. Nucleic Acids Research 39: 8820–8832. PDF or Pubmed

Wallace, A., Filbin, M., Veo, B., McFarland, C., Jankowska-Anyszka, M., Stepinski, J., Darzynkiewicz, E., and R.E. Davis. 2010. The nematode eIF4E/G complex works with a trans-spliced leader stem loop to enable efficient translation of trimethylguanosine-capped RNAs. Mol. Cell. Biol. 30:1958-1970. PDF or Pubmed

Wypijewska, A.,  Bojarska, E., Stepinski, J., Jankowska-Anyszka, M.,  Jemielity, J., Davis, R.E., and E. Darzynkiewicz. 2010. Structural requirements for C. elegans DcpS substrates based on fluorescence and HPLC enzyme kinetic studies. FEBS Letters 277:3003-3013. PDF or Pubmed

Guranowski, A., Wojdyla, A.M., Zimny, J., Wypijewska, A., Kowalska, J., Jemielty, J., Davis, R.E., and P. Bieganowski. 2010. Dual activity of certain HIT proteins: A. thaliana Hint4 and C. elegans DcpS act on adenosine 5'-phosphosulfate as hydrolases (forming AMP) and as phosphorylases (forming ADP). FEBS Letters 584:93-98. PDF or Pubmed

Liu, W., Zhao, R., McFarland, C., Kieft, J., Niedzwiecka, A., Jankowska-Anyszka, M., Stepinski, J., Darzynkiewicz, E., Jones, D.N.M., and R.E. Davis. 2009. Structural insights into parasite eIF4E binding specificity for m7G and m2,2,7G mRNA cap. J. Biol. Chem. 284:31333-331349. PDF or Pubmed

Kowalska, J., Lewdorowicz, M., Zuberek, J., Grudzien-Nogalska, E., Bojarska, J., Stepinski, J., Rhoads, R.E., Darzynkiewicz, E., Davis, R.E. and Jemielity, J. 2008. Synthesis and characterization of mRNA cap analogs containing phosphorothioate substitutions that bind tightly to eIF4E and are resistant to the decapping pyrophosphatase DcpS. RNA. 14:1-14. PDF or Pubmed

Cheng, G., Cohen, L.S., Mikhli, M., Jankowska-Anyszka, M., Stepinski, J., Darzynkiewicz, E., and R.E. Davis. 2007. In vivo translation and stability of trans-spliced mRNAs in nematode embryo. Mol. Biochem. Parasitol. 153:95-106. PDF or Pubmed

Cheng, G. and R.E. Davis. 2007. An improved and secreted luciferase reporter for schistosomes. Mol. Biochem. Parasitol. 155:167-171. PDF or Pubmed

Darzynkiewicz, Z.M., Bojarska E., Kowalska J., Lewdorowicz M., Jemielity J., Kalek K, Stepinski J., Davis R.E. and Edward Darzynkiewicz. 2007. Interaction of human decapping scavenger with 5' mRNA cap analogues: structural requirements for catalytic activity. J. Phys. Cond. Matter. 19:285217-2. PDF

Kalek, M., Jemielity, J., Darzynkiewicz, Z.M., Bojarska, E., Stepinski, J., Stolarski, R., Davis, R.E., and E. Darzynkiewicz. 2006. Enzymatically stable 5' mRNA cap analogs: Synthesis and binding studies with human DcpS decapping Enzyme. Bioorganic and Medicinal Chemistry. 14:3223-3230. PDF or Pubmed

Cheng, G, Cohen, L, Ndegwa, D., and R.E. Davis. 2006. The flatworm spliced leader 3' terminal AUG as a translation initiator methionine. J. Biol. Chem. 281:733-743. PDF or Pubmed

Lall, S, Piano, F., and R. E. Davis. 2005. C. elegans decapping proteins: Localization and functional analysis of Dcp1, Dcp2, and DcpS during embryogenesis. Mol. Biol. Cell. 16:5880-5890k PDF or Pubmed

Cohen, L.S., Mikhli, M., Jiao, X., Kiledjian, M., Kunkel, G., and R.E. Davis. 2005. Dcp2 Decaps m2,2,7GpppN‚ 5' capped RNAs and its activity is sequence and context dependent. Mol. Cell. Biol. 25:8779-8791. PDF or Pubmed

Blumenthal, T. and R. E. Davis. 2004. Exploring nematode diversity. Nat. Genet. 12:1246-124. PDF or Pubmed

Lall, S., Friedman, C., Jankowska-Anyszka, M., Stepinski, J., Darzynkiewicz, E., and R.E. Davis. 2004. Contribution of trans-splicing, 5' leader length, cap-poly(A) synergism, and initiation factors to nematode translation in an Ascaris suum embryo cell-free system. J. Biol. Chem. 279:45573-45585 PDF or Pubmed (JBC Paper of the Week)

Cohen, L.S., Mikhli, M., Friedman, C., Jankowska-Anyszka, M., Stepinski, J., Darzynkiewicz, E., and R.E. Davis. 2004. Nematode m7GpppG and m32,2,7GpppG Decapping: Activities in Ascaris Embryos and Characterization of C. elegans Scavenger DcpS. RNA 10: 1609-1624. PDF or Pubmed

Higazi T.B., Merriweather, A., Shu,L., Davis, R., and T.R. Unnasch. 2002. Brugia malayi:Transient transfection by microinjection and particle bombardment. Expt. Parasit. 100:95-102. PDF or Pubmed

Davis, R.E., A. Parra, P. LoVerde, E. Ribeiro, G. Glorioso, and S. Hodgson. 1999. Transient expression of RNA and DNA in parasitic helminths by using particle bombardment. Proc. Natl. Acad. Sci. USA 96:8867-8892. PDF or Pubmed

Davis, R.E. and S. Hodgson. 1997. Gene linkage and steady state RNAs suggests trans-splicing may be associated with a polycistronic transcript in the flatworm Schistosoma mansoni. Mol. Biochem. Parasitol. 89:25-39. PDF or Pubmed

Davis, R.E. 1997. Surprising diversity and distribution of SL RNAs in flatworms. Mol. Biochem. Parasitol. 87:29-48. PDF or PubMed

Davis, R.E., C. Hardwick, P. Tavernier, S. Hodgson, and  H. Singh. 1995. RNA trans-splicing in flatworms: Analysis of trans-spliced genes and mRNAs in the human parasite, Schistosoma mansoni. J. Biol. Chem. 270:21813-21819. PDF or Pubmed

Davis, R.E., H. Singh, C. Botka, C. Hardwick, A. Meanawy, and J. Villanueva. 1994.  RNA trans-splicing in Fasciola hepatica : Identification of an SL RNA and spliced leader sequences on mRNAs. J. Biol. Chem. 269:20026-20031. PDF or Pubmed

Rajkovic, A., R.E. Davis, J.N. Simonsen and F.M. Rottman. 1990. A spliced leader is present on a subset of mRNAs from the human parasite Schistosoma mansoni. Proc. Natl. Acad. Sci. 87: 8879-8883. PDF or Pubmed

Rajkovic, A., J.N. Simonsen, R.E. Davis and F.M. Rottman.  1989.  Molecular cloning and sequence analysis of 3-hydroxy-3-methylglutaryl coenzyme A reductase from the human parasite Schistosoma mansoni. Proc. Natl. Acad. Sci. 86:8217-8221. PDF or Pubmed

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