Eukaryotic mRNA can be controlled at many different steps. In the nucleus, transcription and mRNA processing are needed to generate mRNAs that can be translated. In the cytoplasm, mature mRNAs can be regulated at the levels of stability, translation and localization. The objective of the proposed work is to understand the molecular mechanisms that regulate mature mRNAs in animal cells. We focus on controls mediated by sequences that lie beyond the termination codon - in the 3'untranslated region (3'UTR) and the poly(A) tail. Regulated changes in poly(A) length occur throughout development, affect the translation and stability of many mRNAs, and occur in many species: We concentrate on a family of novel cytoplasmic poly(A) polymerases, called the GLD-2 family. Members of this family, as well as the proteins with which they interact, are conserved among species, and are critical in a wide range of biological contexts - stem cells, early development and memory, for example. Our ultimate goals are to understand, in molecular terms, how these proteins control the fate and function of mature mRNAs. In the next grant period, we will focus on how GLD-2 PAP acts and is controlled. We continue to emphasize work in Xenopus and early development, and extend our analysis of links between other regulators and GLD-2. We will continue to combine molecular genetics and biochemistry to dissect how GLD-2 and its protein partners function. The broad conservation of these proteins among metazoa, and their presence in most somatic tissues, suggests that our findings will bear broadly on regulation in diverse systems. In focusing sharply on the GLD-2 family, and a few selected biological contexts, we hope to address the broad questions of how 3'UTR controls function, evolve, and coordinate expression of multiple mRNAs.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM031892-26
Application #
8204433
Study Section
Special Emphasis Panel (NSS)
Program Officer
Bender, Michael T
Project Start
1983-04-01
Project End
2012-11-30
Budget Start
2011-12-01
Budget End
2012-11-30
Support Year
26
Fiscal Year
2012
Total Cost
$333,396
Indirect Cost
$98,172
Name
University of Wisconsin Madison
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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