This is a revised proposal. RNA is central to a multitude of important cellular processes and is also unique among nucleic acids in being able to catalyze chemical reactions. Despite its importance, very little is known about the atomic structure of RNA molecules larger than 50 nucleotides. The applicants are interested in the structure of large RNA molecules and hence have focused attention on the RNA component of ribonuclease P (Rnase P). RNase P is the endonuclease responsible for cleavage of the 5' end of pre-tRNA leading to tRNA maturation. Both the Rnase P RNA (P RNA) from Bacillus subtilis and Escherichia coli are formed by two independent domains. Domain I is approximately 150 nucleotides long (about 52 kDa) and is involved in tRNA recognition. The applicants have crystallized domain I from both B. subtilis and E. coli and have started to elucidate their atomic structures. The long term goal of this project is to understand the structure and function of RNase P RNA.
The specific aims of this proposal are: To elucidate the atomic structure of domain I of B. subtilis P RNA. Crystals are already in hand, and they diffract to at least 4.0 A. To improve the crystals of domain I of B. subtilis P RNA to be able to obtain atomic resolution information. To elucidate the structure of domain I of E. coli P RNA (M1 RNA). Preliminary crystals have already been obtained. To compare the structure of domain I from B. subtilis and E. coli to identify the features important for their similarities and differences. The work on P RNA is relevant to other studies of large RNA molecules and, in particular, to the study of catalytic RNA molecules.
| Chan, Clarence W; Kiesel, Benjamin R; Mondragón, Alfonso (2018) Crystal Structure of Human Rpp20/Rpp25 Reveals Quaternary Level Adaptation of the Alba Scaffold as Structural Basis for Single-stranded RNA Binding. J Mol Biol 430:1403-1416 |
| Chetnani, Bhaskar; Mondragón, Alfonso (2013) Structural biology: RNA exerts self-control. Nature 500:279-80 |
| Mondragón, Alfonso (2013) Structural studies of RNase P. Annu Rev Biophys 42:537-57 |
| Chan, Clarence W; Chetnani, Bhaskar; Mondragón, Alfonso (2013) Structure and function of the T-loop structural motif in noncoding RNAs. Wiley Interdiscip Rev RNA 4:507-22 |
| Reiter, Nicholas J; Osterman, Amy K; Mondragón, Alfonso (2012) The bacterial ribonuclease P holoenzyme requires specific, conserved residues for efficient catalysis and substrate positioning. Nucleic Acids Res 40:10384-93 |
| Reiter, Nicholas J; Chan, Clarence W; Mondragón, Alfonso (2011) Emerging structural themes in large RNA molecules. Curr Opin Struct Biol 21:319-26 |
| Reiter, Nicholas J; Osterman, Amy; Torres-Larios, Alfredo et al. (2010) Structure of a bacterial ribonuclease P holoenzyme in complex with tRNA. Nature 468:784-9 |
| Torres-Larios, Alfredo; Swinger, Kerren K; Pan, Tao et al. (2006) Structure of ribonuclease P--a universal ribozyme. Curr Opin Struct Biol 16:327-35 |
| Krasilnikov, Andrey S; Mondragon, Alfonso (2003) On the occurrence of the T-loop RNA folding motif in large RNA molecules. RNA 9:640-3 |
