RNA Polymerase II Elongation Control in Eukaryotes

Abstract

During the 1990s, it became clear that the elongation properties of RNA polymerase II are regulated and the factors responsible play a critical role in controlling gene expression in eukaryotic cells. One set of factors helps RNA polymerase II to negotiate pause and arrest sequences in the template, and to maintain an elongation rate of 1000–1500 nucleotides per minute. The initiation factor TFIIF (transcription initiation factor IIF) reduces RNA polymerase II pause times and stimulates the rate of elongation. The elongation factor S-II or transcription initiation factor IIS (TFIIS) rescues polymerase molecules that are blocked from further elongation at arrest sites. Another set of factors is responsible for an elongation control process that regulates the fraction of initiated polymerases that enter productive elongation to generate messenger RNAs (mRNAs). Negative transcription elongation factors (N-TEFs), such as 5,6-dichlororibofuranosyl benzamidizole (DRB) sensitivity inducing factor (DSIF) and negative elongation factor (NELF), slow the rate of elongation and restrict the polymerase to promoter proximal sequences. The positive transcription elongation factor, P-TEFb, overcomes the effect of the negative factors and allows the production of full-length transcripts. The function of P-TEFb is regulated through interactions with many other transcription factors and the amount of active P-TEFb in the cell is precisely regulated through a reversible inhibition by the small cellular RNA, 7SK.