Regulation of the poly(A) Polymerase Star-PAP by a Nuclear Phosphoinositide Signalosome.
bioRxiv
; 2024 Jul 02.
Article
in En
| MEDLINE
| ID: mdl-39005346
ABSTRACT
Star-PAP is a noncanonical poly(A) polymerase that controls gene expression. Star-PAP was previously reported to bind the phosphatidylinositol 4-phosphate 5-kinase PIPKI⺠and its product phosphatidylinositol 4,5-bisphosphate, which regulate Star-PAP poly(A) polymerase activity and expression of specific genes. Recent studies have revealed a nuclear PI signaling pathway in which the PI transfer proteins PITPâº/ß, PI kinases and phosphatases bind p53 to sequentially modify protein-linked phosphatidylinositol phosphates and regulate its function. Here we demonstrate that multiple phosphoinositides, including phosphatidylinositol 4-monophosphate and phosphatidylinositol 3,4,5-trisphosphate are also coupled to Star-PAP in response to stress. This is initiated by PITPâº/ß binding to Star-PAP, while the Star-PAP-linked phosphoinositides are modified by PI4KIIâº, PIPKIâº, IPMK, and PTEN recruited to Star- PAP. The phosphoinositide coupling enhances the association of the small heat shock proteins HSP27/âºB-crystallin with Star-PAP. Knockdown of the PITPs, kinases, or HSP27 reduce the expression of Star-PAP targets. Our results demonstrate that the PITPs generate Star-PAP-PIPn complexes that are then modified by PI kinases/phosphatases and small heat shock proteins that regulate the linked phosphoinositide phosphorylation and Star-PAP activity in response to stress.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
BioRxiv
Year:
2024
Document type:
Article