This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. mRNA maturation and decay. The stability and lifetime of cellular mRNA depends on pre-mRNA processing and decay pathways. We study early processing events associated with RNA capping including the catalytic steps that are required in eukaryotic organisms to cap the nascent mRNA chain. The 5 triphosphate (pppN) of the mRNA is cleaved by RNA triphosphatase to produce a 5 diphosphate (ppN) mRNA molecule. This reaction product is a substrate for RNA guanylyltransferase in a reaction that transfers GMP from GTP to the 5 diphosphate end of the RNA (GpppN). The guanylate is methylated by RNA (guanine-7) methyltransferase to form the functional m7GpppN cap. Each of the cap-forming activities is essential for cell growth. We are characterizing the structural basis for several enzymes in complex with each other, in complex with RNA and oligonucleotide compounds, and in complex with phosphorylated CTD from RNA polymerase II. RNA decay also plays an important role in RNA metabolism, and we are engaged in studies aimed at elucidating regulatory mechanisms controlling several decay pathways. SUMO. The small ubiquitin-like modifier SUMO regulates nuclear transport, stress response, and signal transduction in eukaryotes, a process that is essential for cell cycle progression in yeast. Analogous to ubiquitin modification, SUMO conjugation occurs on lysine residues and is catalyzed by E1, the SUMO activating enzyme, E2, the SUMO conjugation enzyme, E3-like conjugation cofactors, and proteases that catalyze SUMO processing and deconjugation. SUMO modification does not appear to target proteins for degradation, but rather alters the target protein function through changes in cellular localization, biochemical activation, or through protection from ubiquitin-dependent degradation. We have structurally characterized several components of this system, both alone and in complex with each other. We are currently characterizing the structural basis for additional complexes between E1, E2, E3, SUMO and various substrates and cofactors.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
3P41RR015301-05S1
Application #
7369521
Study Section
Special Emphasis Panel (ZRG1)
Project Start
2005-06-01
Project End
2007-05-31
Budget Start
2005-06-01
Budget End
2007-05-31
Support Year
5
Fiscal Year
2006
Total Cost
$6,664
Indirect Cost
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
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