CstF-64 and 3′-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding PAPα

Kandala, Divya T.; Mohan, Nimmy; Vivekanand, A; Ap, Sudheesh; Reshmi, G.; Laishram, Rakesh S.

doi:10.1093/nar/gky1248

Cited by 1 publication

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“…2A-F ). Star-PAP-PIPKI⍺ complexes were largely nuclear consistent with its role in regulating Star-PAP (Kandala et al , 2019; Koshre et al ., 2021; Laishram, 2018; Mellman et al ., 2008; Sudheesh et al ., 2019), while each of the other Star-PAP complexes were present in the both the nucleus and cytosol. To further establish these interactions, PITP⍺/β, PI4KIIα, IPMK, and PTEN co-IPed with Star-PAP, and their interaction was enhanced by etoposide and DEM ( Fig.…”

Section: Resultsmentioning

confidence: 61%

Regulation of the poly(A) Polymerase Star-PAP by a Nuclear Phosphoinositide Signalosome

Wen,

Chen,

Cryns

et al. 2024

Preprint

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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⍺ 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 PITP⍺/β, 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 PITP⍺/β binding to Star-PAP, while the Star-PAP-linked phosphoinositides are modified by PI4KII⍺, PIPKI⍺, IPMK, and PTEN recruited to Star- PAP. The phosphoinositide coupling enhances the association of the small heat shock proteins HSP27/⍺B-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.

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