Gene type-specific control of pol II transcription elongation

Eukaryotic RNA polymerase II (RNA pol II) transcribes both protein-coding and snRNA genes. A hallmark of RNA pol II that distinguishes it from the other RNA polymerases is the unusual carboxy-terminal domain (CTD) of the large subunit. In mammals, the CTD comprises 52 repeats of the heptapeptide YSPTSPS. In the expression of protein-coding genes, phosphorylation of Ser2 of the CTD heptapeptide repeats by the positive transcription elongation factor b (P-TEFb) is associated with productive transcriptional elongation. However, a number of studies show that P-TEFb is not required for elongation of transcription on snRNA genes, but functions only to activate 3' processing. In addition, we find that Negative Elongation Factor (NELF), which is an important factor in the formation of the elongation checkpoint of protein-coding genes, functions as a termination factor on the U2 snRNA genes. Thus, elongation and transcription termination appear to be controlled differently in the transcription of snRNA and protein-coding genes. In order to understand the molecular mechanism underlying these differences, I have analyzed the association of different RNA pol II elongation factors with the β-actin protein-coding gene and the U2 snRNA genes. The elongation factors TFIIS and FACT associate with both gene types, suggesting that these factors are unlikely to be directly involved in the differential control of elongation. However, I have found that a number of other well-characterized elongation factors are differentially associated with the two gene types. Thus, this analysis highlights key players in the gene-type specific switch to productive elongation of transcription.