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J. Biol. Chem., Vol. 283, Issue 23, 15665-15671, June 6, 2008

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Control of the Timing of Promoter Escape and RNA Catalysis by the Transcription Factor IIB Fingertip^*

From the Department of Chemistry and Biochemistry and The Molecular Biology Institute, University of California, Los Angeles, California 90095

Transcription factor IIB (TFIIB) recruits RNA polymerase II to promoters and inserts a finger domain into its active site, with unknown consequences. Here we show that that the tip of this finger is important for two transcription initiation functions. First, TFIIB acts as a catalytic cofactor for initial RNA bond formation. It does so via a pair of fingertip aspartates that can bind magnesium, placing TFIIB within a family of proteins that insert finger domains to alter the catalytic functions of RNA polymerase. Second, the TFIIB fingertip mediates the timing of the release of TFIIB that is associated with appropriate promoter escape. These initiation requirements may assist in RNA quality control by minimizing functional synthesis when RNA polymerase becomes inappropriately associated with the genome without having been recruited there by TFIIB.

Received for publication, February 22, 2008 , and in revised form, April 9, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grant GM49048. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1.

¹ To whom correspondence should be addressed: 607 Charles E. Young Dr. E., Los Angeles, CA 90095. Fax: 310-206-4038; E-mail: gralla{at}mbi.ucla.edu.

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