Three-way regulation of transcription

Phosphorylation regulates the transition between phases of the RNA polymerase II (RNAPII) transcription cycle. The elongation factor SPT5 is phosphorylated by the CDK9 kinase on a flexible linker and in C-terminal repeat 1 (CTR1) to regulate promoter-proximal pausing and termination. In this study, Sun and Fisher report that the C-terminal repeat 2 (CTR2) region in SPT5 is also phosphorylated by CDK9, and this modification regulates the transcription elongation rate. The researchers investigated the effect of mutating CTR1 or CTR2 in a human colon cancer cell line and found that phosphorylated CTR1 and CTR2 exert opposing effects on elongation — CTR1 accelerates elongation after pause release, whereas CTR2 acts as a brake on RNAPII elongation rate. Despite opposing functions on RNAPII elongation, phosphorylation of CTR1 and CTR2 reinforced gene expression.

This study shows that three-way phosphorylation of SPT5 by CDK9 collectively regulates RNAPII pausing and elongation rate for productive transcription.