The long term objective of this proposal is to understand the function of the mysterious nuclear structures known as coiled bodies (CBs) discovered almost a century ago by Ram""""""""n y Cajal (1903). CBs have been characterized in some detail, but their functions are still unknown. CBs contain a remarkable variety of cellular factors including many U snRNPs that carry out mRNA and rRNA processing reactions, general and gene-specific transcription factors, and cell cycle regulators. [U snRNPs are small nuclear ribonucleoprotein particles containing uridine-rich small nuclear RNAs (U snRNAs).] Remarkably, CBs preferentially associate with chromosomal loci encoding U snRNAs. Thus the same nuclear structure that contains mature U snRNPs associates with the genes that encode the U snRNA components of these snRNPs. This and other accumulating evidence suggest that CBs regulate U snRNP biogenesis, perhaps through a feedback loop in which the endproduct of the biosynthetic pathway (U snRNPs) returns to the site of synthesis of a key snRNP component (the U snRNA genes) to regulate overall snRNP production. The major goal of this proposal is to develop an inducible U2 snRNA gene assay system that will enable me to test the hypothesis that CBs regulate snRNA transcription. As components of the large macromolecular complex called the spliceosome; the U snRNPs obviously play key roles in cell biology and development. However, the importance of proper snRNP biogenesis is best exemplified by the autosomal recessive disorder, spinal muscular atrophy (SMA), which is caused by a defect in snRNP assembly, maturation, or recycling.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM020209-01
Application #
6013810
Study Section
Biological Sciences 2 (BIOL)
Program Officer
Tompkins, Laurie
Project Start
1999-08-01
Project End
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Yale University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520