Most eukaryotic genes are interrupted by introns. The primary transcript must be processed to remove the introns and to join the coding sequence into a contiguous mRNA molecule. Different mRNA molecules can be generated from the same pre-mRNA by alternative splicing when the pre-mRNA contains multiple introns. A prerequisite for the accurate excision of introns from nuclear pre-mRNA is specific recognition and pairing of the correct 5' and 3' sites. Cellular machinery carrying out this highly regulated process involves an ordered assembly of components, including heterogeneous nuclear ribonucleoproteins, small nuclear ribonuclear particles and additional protein factors, known as splicing factors. This large complex is known as the spliceosome. Protein-RNA interaction is an essential mechanism in spliceosome assembly and in regulating alternative splicing, which is known to play an important role in controlling gene expressing during development an differentiation. We will study the structural basis of sequence-specific protein-RNA interactions by splicing factors and hnRNP proteins in both constitutive and alternative pre-mRNA splicing. Our study will lead to the understanding of how these spliceosomal components achieve their function in regulating pre-mRNA splicing at an atomic level.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM055874-05S1
Application #
6712691
Study Section
Molecular Biology Study Section (MBY)
Program Officer
Lewis, Catherine D
Project Start
1998-01-01
Project End
2003-07-31
Budget Start
2002-01-01
Budget End
2003-07-31
Support Year
5
Fiscal Year
2003
Total Cost
$103,222
Indirect Cost
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724
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