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Catalytic RNAs

Gene regulatory RNAs

RNA in signal transduction

RNA-protein interactions

RNA analogs of GFP

Small molecule recognition by RNA

RNA folding and dynamics

Molecular evolution

Methods

 

Ferré-D'Amaré Lab Research > RNA-protein interactions

Many cellular proteins associate with RNAs either transiently or long-term to form ribonucleoprotein (RNP) complexes. Of particular interest have been enzymes that catalyze the post-transcriptional modification of specific uridine residues to pseudouridines. The responsible enzymes, the pseudouridine synthases, are universally distributed in all life forms and their structural analysis revealed important new principles of RNA recognition by proteins including base flipping and recognition through enforced secondary structure. The box H/ACA RNP is a multi-protein pseudouridine synthase that is conserved from archaea to humans, and it is required for a variety of biological processes: post-transcriptional RNA modification, ribosome biogenesis, and telomerase assembly and stability. In humans, mutations in either the RNA or protein subunits of this RNP result in dyskeratosis congenita, a disease that affects actively proliferating tissues (such as skin, intestinal lining and bone marrow –the latter linked to hematopoietic dysfunction). In addition, patients suffer from elevated susceptibility to cancer. We have also successfully exploited RNP formation as strategy to improve the crystallizability of RNAs.

• Baird, N.J., Zhang, J., Hamma, T. & Ferré-D’Amaré, A.R. YbxF and YlxQ are bacterial homologs of L7Ae and bind K-turns but not K-loops. RNA 18, 759-770 (2012). [abstract]

• Ferré-D'Amaré, A.R. Use of the spliceosomal protein U1A to facilitate crystallization and structure determination of complex RNAs Methods 52: 159-167 (2010). [abstract]

• Hoang, C., Chen, J., Vizthum, C.A., Kandel, J.M., Hamilton, C.S. Mueller, E.G. & Ferré-D’Amaré, A.R. Crystal structure of pseudouridine synthase RluA: indirect sequence readout through protein-induced RNA structure. Mol. Cell 24, 535-545 (2006). [abstract]

• Hamma, T., Reichow, S.L., Varani, G., & Ferré-D’Amaré, A.R. The Cbf5-Nop10 complex is a molecular bracket that organizes box H/ACA RNPs. Nature Struct. Mol. Biol. 12, 1101-1107 (2005). [abstract]

• Hoang, C. & Ferré-D'Amaré, A.R. Cocrystal structure of a tRNA Ψ55 pseudouridine synthase: nucleotide flipping by an RNA-modifying enzyme. Cell 107, 929-939 (2001). [abstract]