CstF-64 and 3′-UTR<i>cis</i>-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/gkv1074

Cited by 15 publications

(30 citation statements)

References 59 publications

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“…The mRNAs of these genes are polyadenylated by Star-PAP, a non-canonical poly(A) polymerase. 21 These observations suggest that for some pA sites, the DSE may represent the critical core element that drives cleavage efficiency and directs how the 3′end machinery is assembled at the pA site.…”

Section: Core Cleavage and Polyadenylation Sequence Elementsmentioning

confidence: 94%

“…This Star-PAP mediated selection of pA sites may play a role in the regulation of APA. 21 PABPC1 No obvious cis -element enriched around pA sites regulated by PABPC1, but, like PABPN1, promotes distal pA site usage. Shuttles between the cytoplasm and nucleus and may regulate cytoplasmic polyadenylation.…”

Section: Factors That Regulate Active Apa By Influencing Pa Sites Chomentioning

confidence: 99%

“…A subset of mRNAs are polyadenylated by the non-canonical poly(A) polymerase Star-PAP (see below), which binds an AUA motif in the 3′UTR of its target pre-mRNAs. 21 …”

Section: Core Cleavage and Polyadenylation Sequence Elementsmentioning

confidence: 99%

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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: Core Cleavage and Polyadenylation Sequence Elementsmentioning

confidence: 94%

Section: Factors That Regulate Active Apa By Influencing Pa Sites Chomentioning

confidence: 99%

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Cleavage and polyadenylation: Ending the message expands gene regulation

et al. 2017

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“…Star-PAP targets distinct mRNAs involved in the oxidative-stress response, apoptosis, and cancer, and this targeting is independent of PAPα for the reported mRNAs ( 17 – 20 ). We have demonstrated that Star-PAP specificity for its target mRNAs is driven by a recognition sequence at the 3′-UTR, followed by exclusion of the canonical PAP via a suboptimal downstream sequence (DSE) located on its target mRNA UTR ( 21 ). While Star-PAP functions without certain cleavage factors, such as CstF-64, it requires additional associated proteins ( 17 , 19 , 21 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

“…We have demonstrated that Star-PAP specificity for its target mRNAs is driven by a recognition sequence at the 3′-UTR, followed by exclusion of the canonical PAP via a suboptimal downstream sequence (DSE) located on its target mRNA UTR ( 21 ). While Star-PAP functions without certain cleavage factors, such as CstF-64, it requires additional associated proteins ( 17 , 19 , 21 , 22 ). Moreover, as opposed to the canonical mechanism, Star-PAP directly binds the target mRNA and plays a structural role to help assemble the cleavage and polyadenylation complex ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

Nuclear Phosphatidylinositol-Phosphate Type I Kinase α-Coupled Star-PAP Polyadenylation Regulates Cell Invasion

Sudheesh

Laishram

2018

Molecular and Cellular Biology

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Star-PAP, a nuclear phosphatidylinositol (PI) signal-regulated poly(A) polymerase (PAP), couples with type I PI phosphate kinase α (PIPKIα) and controls gene expression. We show that Star-PAP and PIPKIα together regulate 3′-end processing and expression of pre-mRNAs encoding key anti-invasive factors (KISS1R, CDH1, NME1, CDH13, FEZ1, and WIF1) in breast cancer. Consistently, the endogenous Star-PAP level is negatively correlated with the cellular invasiveness of breast cancer cells. While silencing Star-PAP or PIPKIα increases cellular invasiveness in low-invasiveness MCF7 cells, Star-PAP overexpression decreases invasiveness in highly invasive MDA-MB-231 cells in a cellular Star-PAP level-dependent manner. However, expression of the PIPKIα-noninteracting Star-PAP mutant or the phosphodeficient Star-PAP (S6A mutant) has no effect on cellular invasiveness. These results strongly indicate that PIPKIα interaction and Star-PAP S6 phosphorylation are required for Star-PAP-mediated regulation of cancer cell invasion and give specificity to target anti-invasive gene expression. Our study establishes Star-PAP–PIPKIα-mediated 3′-end processing as a key anti-invasive mechanism in breast cancer.

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