Associate Professor (Initial Appointment: 1986)
Ph.D., Cornell University (1981)
B.S., Spelman College (1974)

Selected References

Synopsis

Our lab is interested in the mechanisms that fine-tune gene expression and that coordinate transcription with other events in pre-mRNA metabolism such as splicing and polyadenylation.  These regulatory processes are important for efficient mRNA production and to generate precise temporal and spatial mRNA distributions in response to developmental and physiological cues.  Our research is focused on the Drosophila suppressor of sable gene (su(s)), which encodes a protein (Su(s)) that negatively regulates gene expression. This gene was initially because loss-of-function su(s) mutations modify the phenotypes of mutant alleles of various genes. Subsequent studies have shown that the null su(s) mutant is less viable than normal.  Furthermore, null mutant males are sterile when reared at low temperatures.  Ectopic overexpression of su(s) is lethal.  In addition, we have recently discovered that su(s) mutants are unusually sensitive to several forms of environmental stress, including heat shock, oxidative stress and osmotic stress.

 The primarily goals of our research have been to define the molecular and biological processes that depend on the activity of Su(s).  This 150 kDa nuclear protein has several structural motifs that are found in other proteins; however, the overall sequence of Su(s) is not highly conserved.  We have shown that two arginine-rich motifs mediate an RNA binding activity of this protein.  Two CCCH zinc fingers within Su(s) may also be involved in RNA binding, but this has not been established yet. We began the process of investigating the function of Su(s) by performing molecular genetic analysis of an insertion mutant allele of the vermilion (v) gene whose phenotype is suppressed, i.e., reverts to the wild-type phenotype, in a su(s) mutant background.  We found that Su(s) blocks production of RNA from the mutant allele and apparently acts at a point where the transcription and pre-mRNA processing pathways converge. 

We have used polytene chromosome immunofluorescence analysis (PCIF) to compare the global chromosomal distribution pattern of Su(s) to known RNA binding and transcription proteins.  This analysis revealed that Su(s) colocalizes with a hypophosphorylated form of RNA polymerase II (Pol II).  Pol II is believed to be in this state during the early phase of transcription, and, thus, this result suggests that Su(s) acts at an early stage in gene expression. 

PCIF analysis has also enabled us to identify other Su(s) target genes, i.e., the ecdysone-induced Sgs4 and ng1 genes and certain heat-shock induced transcription units.  As was seen with the mutant v allele, Su(s) performs a negative regulatory role in modulating the expression of these other target genes.  Our results indicate that Su(s) performs a quality control function in preventing production of aberrant mRNAs and promoting sharp transitions in the off/on state in response to physiological or developmental signals.  We are using these recently identified target genes to investigate further the molecular function of Su(s). Our current hypothesis is that Su(s) regulates either an aspect of pre-mRNA processing that is tightly coupled to transcription or the transcription process itself.  We are currently in the process of testing these ideas.  We also intend to identify interacting components, and to clarify further the role Su(s) plays in modulating environmental stress responses. 

Su(s) is bound in the vicinity of a subset of actively transcribed genes on salivary gland polytene chromosomes.  Two of the most prominent binding sites, 3C and 87C, are illustrated in panels A and C, respectively.  The pictures shown are merged confocal images of chromosomes labeled with antibodies that detect Su(s) (red), RNA Pol II (green) and the DNA stain DAPI (blue). Pol IIa is hypophosphoryated whereas Ser2-P is a hyperphosphorylated form of Pol II.  A high level of Su(s) is present at the 3C region during puff stage (PS) 1-2 and in the 87C region of heat-shocked chromosomes.  The schematic drawings in B and D are maps of genes in the 3C and 87C regions, respectively, where Su(s) is bound.  We have shown that Su(s) regulates expression of Sgs4 and ng in the 3C region and γβ elements at 87C.