The tumor suppressor parafibromin is required for posttranscriptional processing of histone mRNA

Farber, Leslie J.; Kort, Eric J.; Wang, Pengfei; Chen, Jindong; Teh, Bin Tean

doi:10.1002/mc.20591

Cited by 30 publications

(19 citation statements)

References 35 publications

(43 reference statements)

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“…Moreover, in humans the PAF1c subunit Leo1 interacts with Ranbp2, a nuclear pore complex protein (Forler et al 2004; Rozenblatt-Rosen et al 2005). Recently, Farber et al (2010) reported that Cdc73 is required for proper histone mRNA 3′ processing and export to the cytoplasm. Together, these results support the view that PAF1c may have yet an additional function, to facilitate nuclear export of the mRNAs of target genes.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Activators Enhance Polyadenylation of mRNA Precursors

et al. 2011

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Polyadenylation of mRNA precursors is frequently coupled to transcription by RNA polymerase II. Although this coupling is known to involve interactions with the C-terminal domain of the RNA polymerase II largest subunit, the possible role of other factors is not known. Here we show that a prototypical transcriptional activator, GAL4-VP16, stimulates transcription-coupled polyadenylation in vitro. In the absence of GAL4-VP16, specifically initiated transcripts accumulated but little polyadenylation was observed, while in its presence polyadenylation was strongly enhanced. We further show that this stimulation requires the transcription elongation-associated PAF complex (PAF1c), as PAF1c depletion blocked GAL4-VP16-stimulated polyadenylation. Furthermore, knockdown of PAF subunits by siRNA resulted in decreased 3′ cleavage, and nuclear export, of mRNA in vivo. Finally, we show that GAL4-VP16 interacts directly with PAF1c and recruits it to DNA templates. Our results indicate that a transcription activator can stimulate transcription-coupled 3′ processing and does so via interaction with PAF1c.

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Section: Discussionmentioning

confidence: 99%

Transcriptional Activators Enhance Polyadenylation of mRNA Precursors

et al. 2011

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“…For example, the multifunctional PAFc was found to be required for transcription-coupled polyadenylation stimulated by the prototypical transcriptional activator GAL4-VP16 (167). Moreover, the PAFc subunit Cdc73 is essential for proper histone mRNA 3’ processing as well as export to the cytoplasm (168). PAFc likely accomplishes these tasks through recruiting key polyadenylation factors such as the cleavage/polyadenylation specificity factor (CPSF), cleavage stimulation factor (CstF), and symplekin, a scaffolding protein for 3’ processing, to transcribing Pol II (169, 170).…”

Section: Transcription Elongation Coupled Eventsmentioning

confidence: 99%

RNA Polymerase II Elongation Control

Zhou

Li²,

Price³

2012

Annu. Rev. Biochem.

522

633

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Regulation of the elongation phase of transcription by RNA Polymerase II (Pol II) is utilized extensively to generate the pattern of mRNAs needed to specify cell types and to respond to environmental changes. After Pol II initiates, negative elongation factors cause it to pause in a promoter proximal position. These polymerases are poised to respond to the positive transcription elongation factor, P-TEFb, and then enter productive elongation only under the appropriate set of signals to generate full length properly processed mRNAs. Recent global analyses of Pol II and elongation factors, mechanisms that regulate P-TEFb involving the 7SK snRNP, factors that control both the negative and positive elongation properties of Pol II and the mRNA processing events that are coupled with elongation are discussed.

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“…(C) rkr1D (KY2309) and rkr1D sup35-Y351C (KY2306) strains were used for 10-fold dilution analysis on YPD and YPD containing 50 mM CdCl 2 and incubated at 30°for 3 days. and in altered poly(A) site utilization, which produce substrates for mRNA surveillance pathways (Mueller et al 2004;Penheiter et al 2005;Nordick et al 2008), and defects in hPaf1C give rise to aberrant transcripts, which are inefficiently processed or exported (Farber et al 2010;Nagaike et al 2011). In agreement with these earlier observations, we have shown that deletion of RTF1 results in decreased protein product from two nonstop reporters ( Figure 7), presumably because the absence of Rtf1-dependent histone modifications leads to transcriptional alterations and/ or effects on RNA export, stability, or translation.…”

Section: Discussionmentioning

confidence: 99%

“…Depletion of human Paf1C (hPaf1C) subunits impairs mRNA cleavage, polyadenylation, and export to the cytoplasm (Nagaike et al 2011). Additionally, loss of hCdc73 results in aberrantly processed and polyadenylated histone mRNAs (Farber et al 2010). In yeast, deletion of Paf1C subunits leads to decreased poly(A) tail length and alternative poly(A) site usage (Mueller et al 2004;Strawn et al 2009).…”

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confidence: 99%

The Paf1 Complex Subunit Rtf1 Buffers Cells Against the Toxic Effects of [PSI+] and Defects in Rkr1-Dependent Protein Quality Control in Saccharomyces cerevisiae

Klucevsek

Braun²,

Arndt

2012

Genetics

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The Rtf1 subunit of the Paf1 complex is required for specific histone modifications, including histone H2B lysine 123 monoubiquitylation. In Saccharomyces cerevisiae, deletion of RTF1 is lethal in the absence of Rkr1, a ubiquitin-protein ligase involved in the destruction of nonstop proteins, which arise from mRNAs lacking stop codons or translational readthrough into the poly(A) tail. We performed a transposon-based mutagenesis screen to identify suppressors of rtf1D rkr1D lethality and found that a mutation in the gene encoding the protein chaperone Hsp104 rescued viability. Hsp104 plays a role in prion propagation, including the maintenance of [PSI + ], which contributes to the synthesis of nonstop proteins. We demonstrate that rtf1D and rkr1D are synthetically lethal only in the presence of [PSI + ]. The deletion, inactivation, and overexpression of HSP104 or the overexpression of prion-encoding genes URE2 and LSM4 clear [PSI + ] and rescue rtf1D rkr1D lethality. In addition, the presence of [PSI + ] decreases the fitness of rkr1D strains. We investigated whether the loss of RTF1 exacerbates an overload in nonstop proteins in rkr1D [PSI + ] strains but, using reporter plasmids, found that rtf1D decreases nonstop protein levels, indicating that excess nonstop proteins may not be the cause of synthetic lethality. Instead, our data suggest that the loss of Rtf1-dependent histone modifications increases the burden on quality control pathways in cells lacking Rkr1 and containing [PSI + ]. D URING transcription elongation, various proteins modify chromatin in coordination with RNA polymerase II (Pol II) to ensure accurate and efficient transcription of nucleosomal templates (Li et al. 2007). Changes in chromatin include nucleosome remodeling, the exchange of histone variants for canonical histones, and histone modifications such as the methylation, ubiquitylation, and acetylation of lysine (K) residues. The conserved Paf1 complex (Paf1C), which consists of Paf1, Ctr9, Leo1, Cdc73, and Rtf1, associates with Pol II on all actively transcribed genes (Mayer et al. 2010) and couples the modification of histones to transcription elongation (reviewed in Crisucci and Arndt 2011; Jaehning 2010). Paf1C is required for multiple histone modifications associated with active genes, including the monoubiquitylation of H2B K123, a modification for which the Rtf1 subunit of Paf1C plays a prominent role (Ng et al. 2003;Wood et al. 2003;Warner et al. 2007;Tomson et al. 2011). Rad6 is the ubiquitin-conjugating enzyme (E2) for H2B K123 ubiquitylation, while Bre1 is the ubiquitin-protein ligase (E3) (Hwang et al. 2003). This modification is a prerequisite for downstream histone H3 methylation (Dover et al. 2002;Sun and Allis 2002;Ng et al. 2003;Wood et al. 2003). In yeast, loss of H2B K123 ubiquitylation broadly impacts gene expression and chromatin structure (Mutiu et al. 2007;Batta et al. 2011). In humans, errors in Paf1C-dependent histone modifications can lead to aberrant gene expression and tumorigenesis (reviewed in Cris...

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The tumor suppressor parafibromin is required for posttranscriptional processing of histone mRNA

Cited by 30 publications

References 35 publications

Transcriptional Activators Enhance Polyadenylation of mRNA Precursors

Transcriptional Activators Enhance Polyadenylation of mRNA Precursors

RNA Polymerase II Elongation Control

The Paf1 Complex Subunit Rtf1 Buffers Cells Against the Toxic Effects of [PSI+] and Defects in Rkr1-Dependent Protein Quality Control in Saccharomyces cerevisiae

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