The General Transcription Machinery and Preinitiation Complex Formation

Abstract

Transcription of protein-coding genes in eukaryotes is regulated by RNA polymerase II (pol II). By itself, pol II is unable to direct site-specific initiation of transcription and requires a host of accessory proteins, termed general transcription factors (GTFs), to commence basal level transcription dictated by the core promoter elements. The GTFs for pol II-mediated transcription include TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH. The transcription cycle, whether basal or regulated transcription, can be divided into multiple stages: preinitiation complex (PIC) assembly, initiation, promoter clearance, elongation, termination, and reinitiation. Before initiation, TFIID binding to the core promoter marks the beginning for PIC assembly. This is followed by the entry of TFIIA, TFIIB, pol II/TFIIF, TFIIE, and TFIIH, either in a stepwise fashion or as a preassembled pol II holoenzyme complex, to form a stable PIC which is ready to make RNA when ribonucleoside triphosphates and an energy source are provided. Formation of the PIC is a critical and often rate-limiting step in transcriptional regulation. Here we discuss the properties of pol II and each GTF in relation to PIC assembly, which occurs prior to the formation of the first phosphodiester bond in transcription initiation.