P-TEFb, a Cyclin-Dependent Kinase Controlling Elongation by RNA Polymerase II

Abstract

The elongation phase of transcription by RNA polymerase II is one of the many steps during the generation of mature mRNAs that is subject to regulation. Shortly after initiation, RNA polymerase II comes under the control of negative transcription elongation factors, generally termed N-TEFs, and enters abortive elongation (51). During this postinitiation process, only short transcripts are generated that may be prematurely terminated. These short transcripts arise from transcription of many genes, including c-myb, c-myc, c-fos, HSP70, and the human immunodeficiency virus (HIV) long terminal repeat (LTR), and are normally subject to rapid degradation (3, 63). Escape from the action of N-TEF requires the action of at least one positive transcription elongation factor (P-TEF), eventually identified as P-TEFb (52). P-TEFb allows the transition into productive elongation, producing long transcripts from which mRNAs are derived. In this way, the fraction of initiating RNA polymerase II molecules that produce full-length transcripts is controlled by a selection process that occurs early in the elongation phase of the transcription cycle. After the transition is made into productive elongation, the efficiency of elongation may be influenced by additional factors, including S-II, TFIIF, ELL, and elongin (62, 65).