Transfer RNAs are transcribed as precursors with 5'and 3'end extensions which must be removed by processing. In the pre-tRNA maturation pathway, tRNase Z cleaves one nucleotide beyond the 3'end of the acceptor stem, endonucleolytically removing the 3'end trailer. A recognition and binding domain (RBD) is extruded from the body of tRNase Z remote from the active site. A co-crystal structure suggests that the globular head of the RBD principally binds to the elbow (D/T loops) of tRNA, far from the scissile bond. We propose to investigate the RBD of tRNase Z by posing three questions: (1) How does each residue in the head of the RBD contribute to substrate binding and catalysis? (2) Is the RBD an independently folding unit? (3) What are the contacts between the RBD and pre-tRNA? This investigation will shed light on a novel mechanism for substrate recognition. Transfer RNA (tRNA) is central to the process of protein synthesis. Mutations in tRNAs are associated with maternally transmitted mitochondrial diseases and syndromes. Additionally, the gene that encodes tRNase Z, an enzyme in the tRNA maturation pathway, has been associated with an elevated risk of prostate cancer, making the proposed research biomedically relevant.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Continuance Award (SC3)
Project #
3SC3GM084764-02S1
Application #
7936479
Study Section
Special Emphasis Panel (ZGM1-MBRS-2 (MV))
Program Officer
Rivera-Rentas, Alberto L
Project Start
2009-09-30
Project End
2011-05-31
Budget Start
2009-09-30
Budget End
2011-05-31
Support Year
2
Fiscal Year
2009
Total Cost
$131,397
Indirect Cost
Name
York College
Department
Type
DUNS #
620128822
City
Jamaica
State
NY
Country
United States
Zip Code
11451
Wilson, Christopher; Ramai, Daryl; Serjanov, Dmitri et al. (2013) Tethered domains and flexible regions in tRNase Z(L), the long form of tRNase Z. PLoS One 8:e66942
Schaller, A; Desetty, R; Hahn, D et al. (2011) Impairment of mitochondrial tRNAIle processing by a novel mutation associated with chronic progressive external ophthalmoplegia. Mitochondrion 11:488-96
Levinger, Louis; Hopkinson, Angela; Desetty, Rohini et al. (2009) Effect of changes in the flexible arm on tRNase Z processing kinetics. J Biol Chem 284:15685-91