POST TRANSCRIPTIONAL REGULATION--ONCOGENE MESSENGER RNA

Project Details

Description

Our major goal is to understand how mRNA levels for the proto-oncogene c-
myc are regulated, because sustained synthesis of c-myc protein favors cell
growth rather than differentiation, a hallmark of the neoplastic phenotype.
Many proto-oncogene mRNAs exhibit extremely short half lives. The turnover
of these mRNAs is frequently subject to regulatory control. For example,
the decay rates of the mRNA for the proto-oncogene c-myc vary during cell
growth and differentiation. As a result, c-myc mRNA levels are highest
during cell growth and lowest during differentiation. Thus the control of
c-myc mRNA decay rates is an important mechanism regulating c-myc
expression in mammalian cells. We are interested in why c-myc mRNA is
degraded at different rates, how c-myc mRNA turnover is regulated and what
factors are involved in its regulation. We developed a cell-free mRNA
decay system in order to biochemically dissect the mRNA degradation
machinery. Using the cell-free system, we have identified a cytosolic
ribonucleoprotein (RNP) which destabilizes c-myc mRNA without affecting
mRNA metabolism in general. Its activity varies in extracts from cells
depending on cellular rates of translation, growth and stage of
differentiation and correlates with the in vivo decay rate of c-myc mRNA.
We plan to address the following questions: (1) What is the polypeptide
and RNA composition of the RNP? (2) Does it regulate the turnover of other
mRNAs beside c-myc? What is the substrate specificity of the RNP? (3) Do
changes in c-myc mRNA decay rates, induced by changes in translation, cell
growth or differentiation, correlate with quantitative or qualitative
changes in the RNP? Our approach is to purify the RNP to determine its
composition and mRNA substrate specificity in order to understand its role
in c-myc expression.
StatusFinished
Effective start/end date7/1/905/31/15

Funding

  • National Institutes of Health: $226,006.00
  • National Institutes of Health: $322,123.00
  • National Institutes of Health
  • National Institutes of Health: $29,802.00
  • National Institutes of Health: $341,980.00
  • National Institutes of Health: $346,808.00
  • National Institutes of Health
  • National Institutes of Health: $333,625.00
  • National Institutes of Health: $53,247.00
  • National Institutes of Health: $8,019.00
  • National Institutes of Health: $64,611.00
  • National Institutes of Health
  • National Institutes of Health: $344,232.00
  • National Institutes of Health: $186,096.00
  • National Institutes of Health
  • National Institutes of Health: $336,849.00
  • National Institutes of Health
  • National Institutes of Health: $44,730.00
  • National Institutes of Health: $356,071.00
  • National Institutes of Health: $324,449.00
  • National Institutes of Health: $352,594.00
  • National Institutes of Health
  • National Institutes of Health: $57,153.00
  • National Institutes of Health: $59,189.00
  • National Institutes of Health: $335,473.00
  • National Institutes of Health: $342,283.00
  • National Institutes of Health: $56,260.00

ASJC

  • Medicine(all)

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