In vivo requirement of the RNA polymerase II elongation factor elongin A for proper gene expression and development.
A number of transcription factors that increase the catalytic rate of mRNA synthesis by RNA polymerase II (Pol II) have been purified from higher eukaryotes. Among these are the ELL family, DSIF, and the heterotrimeric elongin complex. Elongin A, the largest subunit of the elongin complex, is the transcriptionally active subunit, while the smaller elongin B and C subunits appear to act as regulatory subunits. While much is known about the in vitro properties of elongin A and other members of this class of elongation factors, the physiological role(s) of these proteins remain largely unclear. To elucidate in vivo functions of elongin A, we have characterized its Drosophila homologue (dEloA). dEloA associates with transcriptionally active puff sites within Drosophila polytene chromosomes and exhibits many of the expected biochemical and cytological properties consistent with a Pol II-associated elongation factor. RNA interference-mediated depletion of dEloA demonstrated that elongin A is an essential factor that is required for proper metamorphosis. Consistent with this observation, dEloA expression peaks during the larval stages of development, suggesting that this factor may be important for proper regulation of developmental events during these stages. The discovery of the role of elongin A in an in vivo model system defines the novel contribution played by RNA polymerase II elongation machinery in regulation of gene expression that is required for proper development.
Gerber
Mark
M
Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University Health Sciences Center, 1402 South Grand Blvd., St. Louis, MO 63104, USA.
Eissenberg
Joel C
JC
Kong
Stephanie
S
Tenney
Kristen
K
Conaway
Joan Weliky
JW
Conaway
Ronald C
RC
Shilatifard
Ali
A
D000595:Amino Acid Sequence; D000818:Animals; D002875:Chromosomes / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D000075065:Elongin; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism*
D029721:Drosophila Proteins; D000075065:Elongin; D014157:Transcription Factors; D012319:RNA Polymerase II