Abstract
Transcription elongation is a critical regulatory step in the gene expression cycle. One key regulator of the switch between transcription initiation and elongation is the P-TEFb kinase, which phosphorylates RNA polymerase II (Pol II) and several negative elongation factors to relieve the elongation block at paused promoters to facilitate productive elongation. Here, we highlight recent findings signifying the role of the PPM1G/PP2Cγ phosphatase in activating and maintaining the active transcription elongation state by regulating the availability of P-TEFb and blocking its assembly into the catalytic inactive 7SK small nuclear ribonucleoprotein (snRNP) complex.
Highlights
Studies over the past three decades have provided insights into the importance of transcription regulatory mechanisms in metazoan cells
PPM1G dephosphorylates the T-loop of cyclin-dependent kinase 9 (Cdk9), which uncouples it from the kinase inhibitor Hexim, thereby causing disassembly of the 7SK small nuclear ribonucleoprotein (snRNP) complex, and inducing positive transcription elongation factor b (P-TEFb) activation and polymerase II (Pol II) pause release [29,30] (Figure 4)
A common theme in the field is the identification of signaling components/factors that promote the release of P-TEFb from the 7SK snRNP to relieve transcriptional pausing in what seems to be a highly intricate and dynamic process
Summary
Studies over the past three decades have provided insights into the importance of transcription regulatory mechanisms in metazoan cells. Levels of DSIF and NELF at promoter-proximal regions directly correlate with total Pol II occupancy levels, suggesting that these factors associate with most early elongation complexes [4], and at most Pol II regulated genes implying a general role in controlling pausing [9, 10, 12]. P-TEFb phosphorylates the C-terminal domain (CTD) of the largest subunit of Pol II and negative elongation factors (DSIF and NELF) to promote the escape into productive elongation ( known as transcriptional pause release) [22, 27, 34, 35].
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