Pin1 modulates RNA polymerase II activity during the transcription cycle

Abstract

. Using inducible Pin1 cell lines, we show that Pin1 overexpression is sufficient to release RNAP II from chromatin, which then accumulates in a hyperphosphorylated form in nuclear speckle-associated structures. In vitro transcription assays show that Pin1 inhibits transcription in nuclear extract, while an inactive Pin1 mutant in fact stimulates it. Several assays indicate that the inhibition largely reflects Pin1 activity during transcription initiation and not elongation, suggesting that Pin1 modulates CTD phosphorylation, and RNAP II activity, during an early stage of the transcription cycle.[Keywords: CTD; CTD phosphorylation; Pin1; prolyl isomerase; RNAP II] Supplemental material is available at http://www.genesdev.org.

Pin1 Associates with and Induces Translocation of CRTC2 to the Cytosol, Thereby Suppressing cAMP-responsive Element Transcriptional Activity*

“…1A). Bands (1), (2), and (3) were identified to be DNA-directed RNA polymerase II A, DNA-directed RNA polymerase IIB, and DNA-directed RNA polymerase I by the analysis using LC/MS, which agree with previous reports (23). Then we performed the immunoblotting using many antibodies to detect another protein included in the Pin1-containing complex because many faint bands were visible with silver staining.…”

RNA Polymerase II Phosphorylation and Gene Expression Regulation

“…In any case, both isomerases have important functions in transcription. Therefore, initiation-elongation transition is inhibited by Pin1 [196], whereas Ess1 affects multiple steps, such as initiation, elongation, 3′-end processing, and termination [197,[199][200][201]. In fact, it has been demonstrated that Ess1 promotes Ssu72-dependent function by creating the CTD structural conformation that is recognized by Ssu72 [202], and recently it has been confirmed that isomerization is a key regulator of RNAPII CTD de-phosphorylation at the end of genes [69].…”

“…Yeast Ess1 physically interacts with the CTD [55,197], and it preferentially binds and isomerizes in vitro Ser5P residues [198]. Although Pin1 stimulates RNAPII CTD hyperphosphorylation, which results in transcription repression and inhibition of mRNA splicing [195][196], in vivo studies have proposed that Ess1 promotes RNAPII CTD de-phosphorylation. In any case, both isomerases have important functions in transcription.…”

“…Pin1 in mammals and Ess1 in S. cerevisiae are RNAPII CTD PPIases. Phosphorylated Ser2 and Ser5 match with the pSer-Pro sequence that is recognized by Pin1, and the CTD appears to be its principal target of regulation [195][196]. Pin1 has specificity for phosphorylated Ser/Thr-Pro sequences, and it modulates RNAPII activity during cell cycle at least in part by regulating RNAPII CTD phosphorylation levels [195].…”

Hide and Go Seek: Activation of the Secretory-Specific Poly (A) Site of Igh by Transcription Elongation Factors

“…Phosphorylations of Ser-2, ser-5 and ser-7 of the CTD are the major modifications but cistrans isomerization (Xu and Manley 2007) as well as serine and threonine glycosylation can occur. The multilayered phosphorylation of the CTD is brought about by a series of enzymatic activities during initiation and elongation.…”