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Molecular and Cellular Biology, November 2004, p. 9911-9919, Vol. 24, No. 22
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.22.9911-9919.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

In Vivo Requirement of the RNA Polymerase II Elongation Factor Elongin A for Proper Gene Expression and Development

Mark Gerber,1 Joel C. Eissenberg,1 Stephanie Kong,2 Kristen Tenney,1 Joan Weliky Conaway,2,3 Ronald C. Conaway,2,3 and Ali Shilatifard1,4*

Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University Health Sciences Center,1 St. Louis University Cancer Center, St. Louis,4 Stowers Institute for Medical Research, Kansas City, Missouri,2 Department of Biochemistry and Molecular Biology, Kansas University Medical Center, Kansas City, Kansas3

Received 12 May 2004/ Returned for modification 21 July 2004/ Accepted 5 August 2004

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.

* Corresponding author. Mailing address: Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University Health Sciences Center, 1402 South Grand Blvd., St. Louis, MO 63104. Phone: (314) 977-9228. Fax: (314) 977-5737. E-mail: shilatia{at}slu.edu.

Molecular and Cellular Biology, November 2004, p. 9911-9919, Vol. 24, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.22.9911-9919.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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