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Molecular and Cellular Biology, October 1999, p. 6833-6844, Vol. 19, No. 10
0270-7306/99/$04.00+0

hnRNP U Inhibits Carboxy-Terminal Domain Phosphorylation by TFIIH and Represses RNA Polymerase II Elongation

Myung K. Kim1,* and Vera M. Nikodem2

Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, and Laboratory of Molecular Hematology, National Heart, Lung, and Blood Institute,1 and Mechanisms of Gene Regulation Section, Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases,2 National Institutes of Health, Bethesda, Maryland 20892

Received 1 June 1999/Accepted 5 July 1999

This study describes a potential new function of hnRNP U as an RNA polymerase (Pol II) elongation inhibitor. We demonstrated that a subfraction of human hnRNP U is associated with the Pol II holoenzyme in vivo and as such recruited to the promoter as part of the preinitiation complex. hnRNP U, however, appears to dissociate from the Pol II complex at the early stage of transcription and is therefore absent from the elongating Pol II complex. When tested in the human immunodeficiency virus type 1 transcription system, hnRNP U inhibits elongation rather than initiation of transcription by Pol II. This inhibition requires the carboxy-terminal domain (CTD) of Pol II. We showed that hnRNP U can bind TFIIH in vivo under certain conditions and inhibit TFIIH-mediated CTD phosphorylation in vitro. We find that the middle domain of hnRNP U is sufficient to mediate its Pol II association and its inhibition of TFIIH-mediated phosphorylation and Pol II elongation. The abilities of hnRNP U to inhibit TFIIH-mediated CTD phosphorylation and its Pol II association are necessary for hnRNP U to mediate the repression of Pol II elongation. Based on these observations, we suggest that a subfraction of hnRNP U, as a component of the Pol II holoenzyme, may downregulate TFIIH-mediated CTD phosphorylation in the basal transcription machinery and repress Pol II elongation. With such functions, hnRNP U might provide one of the mechanisms by which the CTD is maintained in an unphosphorylated state in the Pol II holoenzyme.

* Corresponding author. Mailing address: Bldg. 10, Room 7D11, Laboratory of Molecular Hematology, NHLBI, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892. Phone: (301) 594-2924. Fax: (301) 496-9985. E-mail: kimm{at}gwgate.nhlbi.nih.gov.

Molecular and Cellular Biology, October 1999, p. 6833-6844, Vol. 19, No. 10
0270-7306/99/$04.00+0


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