The myosin heavy chain (MHC) gene of Drosophila is an excellent model system for investigating a gene whose transcription is complex and developmentally regulated. The MHC gene of Drosophila is single-copy, however, four messenger RNAs are transcribed from this gene. We have demonstrated that these mRNAs are developmentally expressed and differ in their structure at their 3' ends. Furthermore, two mRNAs result from developmentally regulated alternate splicing. We have identified a transcriptional unit which is adjacent to the MHC gene. We can detect mRNA expressed from this gene in the two stages of development when the MHC gene is maximally expressed. Preliminary evidence indicates that five dominant flightless mutations result from DNA rearrangements within or near this adjacent gene. We are also using oligonucleotide probes to search for MHC related sequences in an attempt to isolate a cytoplasmic MHC gene. The research is significant in several ways. First, the mechanisms involved in the developmental expression and/or alternate splicing of transcripts from a single copy gene are not well understood. An investigation of the Drosophila MHC gene may provide information on how these processes are regulated. Second, we propose to characterize in detail a transcriptional unit which is adjacent to the MHC gene. An analysis of this gene and the flightless mutations which map at or near this gene may ultimately contribute to our understanding of dysfunctions caused by mutations. Finally, we propose to attempt to isolate a Drosophila cytoplasmic MHC gene(s). Accumulating evidence suggests that cytoplasmic MHC genes are diverged in DNA sequence and may not be detectable with muscle gene probes. The isolation and characterization of a cytoplasmic gene should contribute to our knowledge of how these genes are related both at the DNA and protein sequence level.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033297-05
Application #
3282826
Study Section
Molecular Biology Study Section (MBY)
Project Start
1984-04-01
Project End
1990-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106