DSEF-1 is a member of the hnRNP H family of RNA-binding proteins and stimulates pre-mRNA cleavage and polyadenylation in vitro

Bagga, Paramjeet S.; Arhin, George K.; Wilusz, Jeffrey

doi:10.1093/nar/26.23.5343

Cited by 83 publications

(84 citation statements)

References 47 publications

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“…Since hnRNP H/F was shown by us (Millevoi et al 2009) and others (Bagga et al 1998;Alkan et al 2006;Dalziel et al 2007) to bind G-rich sequences and plays a role in 39-end processing, we analyzed whether this factor was able to bind the G-rich regulatory element at the p53 pA signal. The G-rich sequence located downstream from the SV40 pA signal that binds hnRNP H/F (Bagga et al 1998;Alkan et al 2006) and forms a G4 (Supplemental Fig. 5) served as positive control.…”

Section: Resultsmentioning

confidence: 99%

“…These findings support a model whereby DNA damage-induced hnRNP H/F expression promotes its association with the p53 G4, resulting in maintained 39-end processing efficiency. This can occur by recruiting factors that are essential for the cleavage and pA reaction; namely, CstF (Bagga et al 1998;Chen and Wilusz 1998) and poly(A) polymerase (PAP) (Millevoi et al 2009). Since DNA damage induces CstF sequestration in complexes with BRCA1/BARD1 Manley 1999, 2001), RNA Pol II (Kleiman et al 2005), and PARN (Cevher et al 2010), which inhibit 39-end processing, the function of hnRNP H/F in DNA-damaged cells could be to prevent CstF from being hijacked in alternative protein complexes.…”

Section: Hnrnp H/f Regulates P53 Expression and Function In Apoptosismentioning

confidence: 99%

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Essential role for the interaction between hnRNP H/F and a G quadruplex in maintaining p53 pre-mRNA 3′-end processing and function during DNA damage

Decorsière¹,

Cayrel²,

Vagner³

et al. 2011

Genes Dev.

156

155

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Following DNA damage, mRNA 39-end formation is inhibited, contributing to repression of mRNA synthesis. Here we investigated how DNA-damaged cells accomplish p53 mRNA 39-end formation when normal mechanisms of pre-mRNA 39-end processing regulation are inhibited. The underlying mechanism involves the interaction between a G-quadruplex structure located downstream from the p53 cleavage site and hnRNP H/F. Importantly, this interaction is critical for p53 expression and contributes to p53-mediated apoptosis. Our results uncover the existence of a specific rescue mechanism of 39-end processing regulation allowing stress-induced p53 accumulation and function in apoptosis.

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Section: Resultsmentioning

confidence: 99%

Section: Hnrnp H/f Regulates P53 Expression and Function In Apoptosismentioning

confidence: 99%

Essential role for the interaction between hnRNP H/F and a G quadruplex in maintaining p53 pre-mRNA 3′-end processing and function during DNA damage

Decorsière¹,

Cayrel²,

Vagner³

et al. 2011

Genes Dev.

156

155

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“…BTG influences substrates of this methylation pathway including heterogeneous nuclear ribonucleoproteins (hnRNP), which was generally lower in expression in the goodrisk group. hnRNP H1 influences pre-mRNA processing, and its role in cancer is unclear; however, hnRNP H1 has been identified as a protein that binds to the negative regulator spicing element of the Rous Sarcoma Virus (25,26), and also binds a G-rich element downstream of the core SV40 late polyadenylation signal and stimulates 3Ј processing (27). These data suggest that hnRNP H1 could modulate late viral element activity in two known carcinogenic viruses, of which one (SV40) has now been implicated in the pathogenesis of MPM (4).…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiles Predict Survival and Progression of Pleural Mesothelioma

Pass

Liu²,

Wali

et al. 2004

Clinical Cancer Research

112

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Purpose: Clinical outcomes for malignant pleural mesothelioma (MPM) patients having surgery are imprecisely predicted by histopathology and intraoperative staging. We hypothesized that gene expression profiles could predict time to progression and survival in surgically cytoreduced pleural mesothelioma of all stages.Experimental Design: Gene expression analyses from 21 MPM patients having cytoreductions and identical postoperative adjuvant therapy were performed using the U95 Affymetrix gene chip. Using both dChip and SAM, neural networks constructed a common 27 gene classifier, which was associated with either the high-risk and low-risk group of patients. Data were validated using real-time PCR and immunohistochemical staining. The 27 gene classifier was also used for validation in a separate set of 17 MPM patients from another institution.Results: The groups predicted by the gene classifier recapitulated the actual time to progression and survival of the test set with 95.2% accuracy using 10-fold cross-validation. Clinical outcomes were independent of histology, and heterogeneity of progression and survival in early stage patients was defined by the classifier. The gene classifier had a 76% accuracy in the separate validation set of MPMs.Conclusions: These data suggest that pretherapy gene expression analysis of mesothelioma biopsies may predict which patients may benefit from a surgical approach.

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“…They have been found to be associated with nuclear-matrix proteins (19). hnRNP HЈ has been implicated in pre-mRNA 3Ј end formation (20), whereas hnRNP H is involved in splicing regulation as part of the intronic splicing enhancer complex in the c-src neuronal specific N1 exon (21) and through binding to the exon 7 exonic splicing silencer of the rat ␤-tropomyosin gene (22). hnRNP 2H9 is the most recently identified member of this family, and little is known about its functions except for its role in the splicing arrest induced by heat shock (14,23).…”

mentioning

confidence: 99%

Determination of the RNA Binding Specificity of the Heterogeneous Nuclear Ribonucleoprotein (hnRNP) H/H′/F/2H9 Family

Caputi

Zahler

2001

Journal of Biological Chemistry

192

176

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Members of the heterogeneous nuclear ribonucleoprotein (hnRNP) H protein family, H, H, F, and 2H9, are involved in pre-mRNA processing. We analyzed the assembly of these proteins from splicing extracts onto four RNA regulatory elements as follows: a high affinity hnRNP A1-binding site (WA1), a sequence involved in Rev-dependent export (p17gag INS), an exonic splicing silencer from the ␤-tropomyosin gene, and an intronic splicing regulator (downstream control sequence (DCS) from the c-src gene. The entire family binds the WA1, instability (INS), and ␤-tropomyosin substrates, and the core-binding site for each is a run of three G residues followed by an A. Transfer of small regions containing this sequence to a substrate lacking hnRNP H binding activity is sufficient to promote binding of all family members. The c-src DCS has been shown to assemble hnRNP H, not hnRNP F, from HeLa cell extracts, and we show that hnRNP 2H9 does not bind this element. The DCS contains five G residues followed by a C. Mutation of the C to an A changes the specificity of the DCS from a substrate that binds only hnRNP H/H to a binding site for all hnRNP H family members. We conclude that the sequence GGGA is recognized by all hnRNP H family proteins.Some proteins of the heterogeneous nuclear ribonucleoprotein (hnRNP) 1 class were initially described as components of a nucleosome-like structure that protects and organizes nascent RNA polymerase II transcripts (1-3). Our understanding of hnRNP functions has broadened from this purely structural vision to include multiple aspects of mRNA biogenesis such as transcription, splicing, capping, polyadenylation, nuclear transport, and mRNA stability. More than 30 hnRNPs have been identified so far. Many hnRNPs have a modular structure characterized by one or more RNA binding domains and by one or more auxiliary domains that are frequently enriched in a few amino acids, mainly glycines. The RNA recognition motif (RRM), the arginine-rich motif, the KH domain, and the RGG box are some of the main motifs that are found in hnRNP proteins (4).The precise roles of hnRNP proteins in gene expression are likely to be reflected by their RNA binding specificity. Therefore, it is important to have a clear understanding of the RNA binding specificities and affinities of the different family members. Early studies demonstrated that several hnRNPs have affinities for immobilized ribohomopolymers such as poly(G) bound by hnRNPs E, H, F, and M, poly(C) bound by hnRNPs K and J, and poly(U) bound by hnRNPs C and M (5). Subsequently, several hnRNPs were observed to bind specific RNA sequences by UV-mediated cross-linking. Furthermore, utilizing a selection and amplification approach from pools of random RNAs, high affinity binding sequences for hnRNPs A1 (6) and C (7), have been identified. The binding properties of hnRNP A1 are the best characterized so far. Several reports (1, 8 -12) have shown that hnRNP A1 and other members of the hnRNP A/B group (hnRNP A1b, A2, and B1) share common RNA substrate specificities...

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DSEF-1 is a member of the hnRNP H family of RNA-binding proteins and stimulates pre-mRNA cleavage and polyadenylation in vitro

Cited by 83 publications

References 47 publications

Essential role for the interaction between hnRNP H/F and a G quadruplex in maintaining p53 pre-mRNA 3′-end processing and function during DNA damage

Essential role for the interaction between hnRNP H/F and a G quadruplex in maintaining p53 pre-mRNA 3′-end processing and function during DNA damage

Gene Expression Profiles Predict Survival and Progression of Pleural Mesothelioma

Determination of the RNA Binding Specificity of the Heterogeneous Nuclear Ribonucleoprotein (hnRNP) H/H′/F/2H9 Family

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