Poly(A) polymerase (PAP) diversity in gene expression – Star‐PAP vs canonical PAP

Laishram, Rakesh S.

doi:10.1016/j.febslet.2014.05.029

Cited by 45 publications

(59 citation statements)

References 215 publications

(391 reference statements)

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“…A prominent non-canonical PAP called Star-PAP, controls the polyadenylation of a subset of mRNAs that encode for proteins that are associated with DNA damage induced apoptosis and stress responses. 91 …”

Section: The Core Poly(a) Machinerymentioning

confidence: 99%

Cleavage and polyadenylation: Ending the message expands gene regulation

et al. 2017

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Cleavage and polyadenylation (pA) is a fundamental step that is required for the maturation of primary protein encoding transcripts into functional mRNAs that can be exported from the nucleus and translated in the cytoplasm. 3′end processing is dependent on the assembly of a multiprotein processing complex on the pA signals that reside in the pre-mRNAs. Most eukaryotic genes have multiple pA signals, resulting in alternative cleavage and polyadenylation (APA), a widespread phenomenon that is important to establish cell state and cell type specific transcriptomes. Here, we review how pA sites are recognized and comprehensively summarize how APA is regulated and creates mRNA isoform profiles that are characteristic for cell types, tissues, cellular states and disease.

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Section: The Core Poly(a) Machinerymentioning

confidence: 99%

Cleavage and polyadenylation: Ending the message expands gene regulation

et al. 2017

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“…Some of the important factors include cleavage and polyadenylation specificity factor (CPSF), cleavage stimulatory factor (CstF), cleavage factor Im, IIm, symplekin, poly(A) binding protein (PABP) and PAP ( 5 – 9 ). Poly (A) tail at the 3′-end of an mRNA is essential for its stability, translation and export of the transcript from the nucleus to the cytoplasm ( 2 , 5 , 10 ). Polyadenylation activity of a PAP is regulated by a number of factors including phosphorylation status ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation regulates the Star-PAP-PIPKIα interaction and directs specificity toward mRNA targets

Mohan

Francis

et al. 2015

Nucleic Acids Res

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Star-PAP is a nuclear non-canonical poly(A) polymerase (PAP) that shows specificity toward mRNA targets. Star-PAP activity is stimulated by lipid messenger phosphatidyl inositol 4,5 bisphoshate (PI4,5P2) and is regulated by the associated Type I phosphatidylinositol-4-phosphate 5-kinase that synthesizes PI4,5P2 as well as protein kinases. These associated kinases act as coactivators of Star-PAP that regulates its activity and specificity toward mRNAs, yet the mechanism of control of these interactions are not defined. We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKIα interaction. We show that S6 is phosphorylated by CKIα within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIα. Unlike the CKIα mediated phosphorylation at the catalytic domain, Star-PAP S6 phosphorylation is insensitive to oxidative stress suggesting a signal mediated regulation of CKIα activity. S6 phosphorylation together with coactivator PIPKIα controlled select subset of Star-PAP target messages by regulating Star-PAP-mRNA association. Our results establish a novel role for phosphorylation in determining Star-PAP target mRNA specificity and regulation of 3′-end processing.

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“…5, 6, 7 Star-PAP regulates the expression of target genes involved in various cellular processes, such as oxidative response and apoptosis, through processing their mRNAs. 8, 9, 10 However, the physiological and pathological roles of Star-PAP largely remain unknown. Recently, it was reported that Star-PAP inhibits the lipogenesis and thus the cell proliferation in osteosarcoma cells in vitro .…”

mentioning

confidence: 99%

Star-PAP, a poly(A) polymerase, functions as a tumor suppressor in an orthotopic human breast cancer model

Gong

Zhou

et al. 2017

Cell Death Dis

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Star-PAP is a noncanonical poly(A) polymerase and required for the expression of a select set of mRNAs. However, the pathological role of Star-PAP in cancer largely remains unknown. In this study, we observed decreased expression of Star-PAP in breast cancer cell lines and tissues. Ectopic Star-PAP expression inhibited proliferation as well as colony-forming ability of breast cancer cells. In breast cancer patients, high levels of Star-PAP correlated with an improved prognosis. Moreover, by regulating the expression of BIK (BCL2-interacting killer), Star-PAP induced apoptosis of breast cancer cells through the mitochondrial pathway. The growth of breast cancer xenografts in NOD/SCID mice was also inhibited by the doxycycline-induced Star-PAP overexpression. Furthermore, Star-PAP sensitized breast cancer cells to chemotherapy drugs both in vitro and in vivo. In mammary epithelial cells, Star-PAP knockdown partially transformed these cells and induced them to undergo epithelial–mesenchymal transition (EMT). These findings suggested that Star-PAP possesses tumor-suppressing activity and can be a valuable target for developing new cancer therapeutic strategies.

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Poly(A) polymerase (PAP) diversity in gene expression – Star‐PAP vs canonical PAP

Cited by 45 publications

References 215 publications

Cleavage and polyadenylation: Ending the message expands gene regulation

Cleavage and polyadenylation: Ending the message expands gene regulation

Phosphorylation regulates the Star-PAP-PIPKIα interaction and directs specificity toward mRNA targets

Star-PAP, a poly(A) polymerase, functions as a tumor suppressor in an orthotopic human breast cancer model

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