The Prolyl Isomerase Pin1 Targets Stem-Loop Binding Protein (SLBP) To Dissociate the SLBP-Histone mRNA Complex Linking Histone mRNA Decay with SLBP Ubiquitination

Krishnan, Nithya; Lam, Tu Kiet T.; Fritz, Andrew J.; Rempinski, Donald; O’Loughlin, Kieran L.; Minderman, Hans; Berezney, Ronald; Marzluff, William F.; Thapar, Roopa

doi:10.1128/mcb.00382-12

Cited by 40 publications

(95 citation statements)

References 72 publications

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“…This dephosphorylation releases SLBP from the mRNA in the cytoplasm. Pin1 is also involved in SLBP polyubiquitination by interacting with Ser20 and Ser23 in the N-terminus of SLBP [16]. …”

Section: Introductionmentioning

confidence: 99%

A Potential New Mechanism of Arsenic Carcinogenesis: Depletion of Stem-Loop Binding Protein and Increase in Polyadenylated Canonical Histone H3.1 mRNA

Brocato

Chen

Liu

et al. 2015

Biol Trace Elem Res

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Canonical histones are synthesized with a peak in S-phase, whereas histone variants are formed throughout the cell cycle. Unlike messenger RNA (mRNA) for all other genes with a poly(A) tail, canonical histone mRNAs contain a stem-loop structure at their 3’-ends. This stem-loop structure is the binding site for the stem-loop binding protein (SLBP), a protein involved in canonical histone mRNA processing. Recently, we found that arsenic depletes SLBP by enhancing its proteasomal degradation and epigenetically silencing the promoter of the SLBP gene. The loss of SLBP disrupts histone mRNA processing and induces aberrant polyadenylation of canonical histone H3.1 mRNA. Here, we present new data supporting the idea that the lack of SLBP allows the H3.1 mRNA to be polyadenylated using the downstream poly(A) signal. SLBP was also depleted in arsenic-transformed bronchial epithelial cells (BEAS-2B), which led us to hypothesize the involvement of SLBP and polyadenylated H3.1 mRNA in carcinogenesis. Here, for the first time, we report that overexpression of H3.1 polyadenylated mRNA and knockdown of SLBP enhances anchorage-independent cell growth. A pcDNA-H3.1 vector with a poly(A) signal sequence was stably transfected into BEAS-2B cells. Polyadenylated H3.1 mRNA and exogenous H3.1 protein levels were significantly increased in cells containing the pcDNA-H3.1 vector. A soft agar assay revealed that cells containing the vector formed significantly higher numbers of colonies compared to wild-type cells. Moreover, small hairpin RNA for SLBP (shSLBP) was used to knockdown the expression of SLBP. Cells stably transfected with the shSLBP vector grew significantly more colonies in soft agar than cells transfected with a control vector. This data suggests that upregulation of polyadenylated H3.1 mRNA holds potential as a mechanism to facilitate carcinogenesis by toxicants such as arsenic that deplete SLBP.

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“…This dephosphorylation releases SLBP from the mRNA in the cytoplasm. Pin1 is also involved in SLBP polyubiquitination by interacting with Ser20 and Ser23 in the N-terminus of SLBP [16]. …”

Section: Introductionmentioning

confidence: 99%

A Potential New Mechanism of Arsenic Carcinogenesis: Depletion of Stem-Loop Binding Protein and Increase in Polyadenylated Canonical Histone H3.1 mRNA

Brocato

Chen

Liu

et al. 2015

Biol Trace Elem Res

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“…Therefore, although differences in gene expression between WT and dKO DCs are at least partly linked to proteasomal activity, these cannot be ascribed to differences in the total abundance or localization of proteasomes and are likely due to differences in proteasome composition. IPs do not affect mRNA stability and have a minimal influence on mRNA maturation Because factors involved in both mRNA stability and splicing are regulated by ubiquitylation and proteasomal degradation (30)(31)(32), we wished to compare the stability of transcripts overexpressed in WT or in dKO DCs following treatment with actinomycin D (Fig. 3A, 3B).…”

Section: The Effect Of Ips On Gene Expression Is Cell Autonomousmentioning

confidence: 99%

Immunoproteasomes Shape the Transcriptome and Regulate the Function of Dendritic Cells

Verteuil

Rouette

Hardy

et al. 2014

The Journal of Immunology

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By regulating protein degradation, constitutive proteasomes (CPs) control practically all cellular functions. In addition to CPs, vertebrates express immunoproteasomes (IPs). The major nonredundant role ascribed to IPs is their enhanced ability to generate antigenic peptides. We report that CPs and IPs differentially regulate the expression of >8000 transcripts in maturing mouse dendritic cells (DCs) via regulation of signaling pathways such as IFN regulatory factors, STATs, and NF-κB. IPs regulate the transcription of many mRNAs and maturation of a few of them. Moreover, even when engineered to present optimal amounts of antigenic peptide, IP-deficient DCs are inefficient for in vivo T cell priming. Our study shows that the role of IPs in DCs is not limited to Ag processing and reveals a major nonredundant role for IPs in transcription regulation. The dramatic effect of IPs on the transcriptional landscape could explain the various immune and nonimmune phenotypes observed in vertebrates with IP deficiency or mutations.

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“…While the upregulation of SLBP has been studied in some extent and involves changes in SLBP translation, posttranscriptional modifications, and turnover (15)(16)(17)(18), no details are known about the cell cycle regulation of HLF. As mentioned above, only part of CstF is present in the HLF.…”

mentioning

confidence: 99%

CstF64: Cell Cycle Regulation and Functional Role in 3′ End Processing of Replication-Dependent Histone mRNAs

Romeo

Griesbach

Schümperli

2014

Molecular and Cellular Biology

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The 3= end processing of animal replication-dependent histone mRNAs is activated during G 1 /S-phase transition. The processing site is recognized by stem-loop binding protein and the U7 snRNP, but cleavage additionally requires a heat-labile factor (HLF), composed of cleavage/polyadenylation specificity factor, symplekin, and cleavage stimulation factor 64 (CstF64). Although HLF has been shown to be cell cycle regulated, the mechanism of this regulation is unknown. Here we show that levels of CstF64 increase toward the S phase and its depletion affects histone RNA processing, S-phase progression, and cell proliferation. Moreover, analyses of the interactions between CstF64, symplekin, and the U7 snRNP-associated proteins FLASH and Lsm11 indicate that CstF64 is important for recruiting HLF to histone precursor mRNA (pre-mRNA)-resident proteins. Thus, CstF64 is central to the function of HLF and appears to be at least partly responsible for its cell cycle regulation. Additionally, we show that misprocessed histone transcripts generated upon CstF64 depletion mainly accumulate in the nucleus, where they are targets of the exosome machinery, while a small cytoplasmic fraction is partly associated with polysomes.

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The Prolyl Isomerase Pin1 Targets Stem-Loop Binding Protein (SLBP) To Dissociate the SLBP-Histone mRNA Complex Linking Histone mRNA Decay with SLBP Ubiquitination

Cited by 40 publications

References 72 publications

A Potential New Mechanism of Arsenic Carcinogenesis: Depletion of Stem-Loop Binding Protein and Increase in Polyadenylated Canonical Histone H3.1 mRNA

A Potential New Mechanism of Arsenic Carcinogenesis: Depletion of Stem-Loop Binding Protein and Increase in Polyadenylated Canonical Histone H3.1 mRNA

Immunoproteasomes Shape the Transcriptome and Regulate the Function of Dendritic Cells

CstF64: Cell Cycle Regulation and Functional Role in 3′ End Processing of Replication-Dependent Histone mRNAs

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