hnRNP H1 and intronic G runs in the splicing control of the human rpL3 gene

Russo, Annapina; Siciliano, Gabriele; Catillo, Morena; Gentilini, Chiara; Amoresano, Angela; Pucci, Piero; Pietropaolo, C; Russo, Giulia

doi:10.1016/j.bbagrm.2010.01.008

Cited by 36 publications

(48 citation statements)

References 34 publications

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“…In addition, the AR-independent induction of PSA promoter activity by hnRNPH1 in the presence of DHT suggests it may directly bind specific DNA sequences to regulate transcription. The hnRNPH1 is implicated as a trans-acting factor by direct binding to DNA sequences (37) and estrogen response element (38). This new role was also exhibited by other hnRNP members, including hnRNPA1 (39) and hnRNPK (40), primarily via binding DNA Matrix Attachment Regions (MAR), specific chromatin DNA sequences that interact with NM, and initiate transcription (41).…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer

Yang

Jia

Kim

et al. 2016

Clinical Cancer Research

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Purpose: The causes of disproportionate incidence and mortality of prostate cancer among African Americans (AA) remain elusive. The purpose of this study was to investigate the mechanistic role and assess clinical utility of the splicing factor heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) in prostate cancer progression among AA men.Experimental Design: We employed an unbiased functional genomics approach coupled with suppressive subtractive hybridization (SSH) and custom cDNA microarrays to identify differentially expressed genes in microdissected tumors procured from age-and tumor grade-matched AA and Caucasian American (CA) men. Validation analysis was performed in independent cohorts and tissue microarrays. The underlying mechanisms of hnRNPH1 regulation and its impact on androgen receptor (AR) expression and tumor progression were explored.Results: Aberrant coexpression of AR and hnRNPH1 and downregulation of miR-212 were detected in prostate tumors and correlate with disease progression in AA men compared with CA men. Ectopic expression of miR-212 mimics downregulated hnRNPH1 transcripts, which in turn reduced expression of AR and its splice variant AR-V7 (or AR3) in prostate cancer cells. hnRNPH1 physically interacts with AR and steroid receptor coactivator-3 (SRC-3) and primes activation of androgen-regulated genes in a ligand-dependent and independent manner. siRNA silencing of hnRNPH1 sensitized prostate cancer cells to bicalutamide and inhibited prostate tumorigenesis in vivo.Conclusions: Our findings define novel roles for hnRNPH1 as a putative oncogene, splicing factor, and an auxiliary AR coregulator. Targeted disruption of the hnRNPH1-AR axis may have therapeutic implications to improve clinical outcomes in patients with advanced prostate cancer, especially among AA men.

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Section: Discussionmentioning

confidence: 99%

Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer

Yang

Jia

Kim

et al. 2016

Clinical Cancer Research

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“…To this purpose, a ChIp experiment in condition of mythramycin A (MTM) decay (AS-NMD). 24,25 In this paper, we demonstrate that rpL3 is a positive regulator of p21 expression. We show that rpL3 is able to modulate the protein amounts of p21 through a novel pathway independent from p53 involving Sp1 and NPM.…”

Section: Human Rpl3 Induces G 1 /S Arrest or Apoptosis By Modulating P21mentioning

confidence: 99%

Human rpL3 induces G₁/S arrest or apoptosis by modulating p21^waf1/cip1 levels in a p53-independent manner

Russo

Esposito²,

Catillo³

et al. 2012

Cell Cycle

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104

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“…1B shows the most highly enriched motifs around the hnRNP H1 iCLIP sites in 3 0 UTR, 5 0 UTR, coding sequence and introns. Individual studies of hnRNP H1 function in specific examples of splicing have identified functional sites as containing either a poly-G run of varying length, 16 or the tetramer (T/G)GGG. 15 Genome-wide profiles have favored the former, correlating longer poly-G stretches with more confident changes in splicing, 6 and interspersion or termination of the binding site by adenosine.…”

Section: Binding Site Characteristicsmentioning

confidence: 99%

“…15 Intron retention events have also been ascribed to the activities of hnRNP H1, such as the negative feedback control of the rpL3 and U11-48K premRNAs. 16,17 In both cases, hnRNP H1-mediated alternative splicing causes the retention of introns containing premature termination codons (PTC). The presence of the PTC in the transcript decreases its stability and leads to its degradation by the nonsense-mediated decay pathway.…”

Section: Introductionmentioning

confidence: 99%

“…The presence of the PTC in the transcript decreases its stability and leads to its degradation by the nonsense-mediated decay pathway. 16,17 Moreover, hnRNP H1 has been associated with leukemia chemo-resistance via its impact on thymidine phosphorylase (TP) splicing. 18 In addition to these targeted analyses, genome-wide studies have revealed hnRNP H1s role, in conjunction with hnRNP F, in promoting both exon inclusion and skipping.…”

Section: Introductionmentioning

confidence: 99%

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High-throughput analyses of hnRNP H1 dissects its multi-functional aspect

et al. 2016

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ABSTRACThnRNPs are polyvalent RNA binding proteins that have been implicated in a range of regulatory roles including splicing, mRNA decay, translation, and miRNA metabolism. A variety of genome wide studies have taken advantage of methods like CLIP and RIP to identify the targets and binding sites of RNA binding proteins. However, due to the complex nature of RNA-binding proteins, these studies are incomplete without assays that characterize the impact of RBP binding on mRNA target expression. Here we used a suite of high-throughput approaches (RIP-Seq, iCLIP, RNA-Seq and shotgun proteomics) to provide a comprehensive view of hnRNP H1s ensemble of targets and its role in splicing, mRNA decay, and translation. The combination of RIP-Seq and iCLIP allowed us to identify a set of 1,086 high confidence target transcripts. Binding site motif analysis of these targets suggests the TGGG tetramer as a prevalent component of hnRNP H1 binding motif, with particular enrichment around intronic hnRNP H1 sites. Our analysis of the target transcripts and binding sites indicates that hnRNP H1s involvement in splicing is 2-fold: it directly affects a substantial number of splicing events, but also regulates the expression of major components of the splicing machinery and other RBPs with known roles in splicing regulation. The identified mRNA targets displayed function enrichment in MAPK signaling and ubiquitin mediated proteolysis, which might be main routes by which hnRNP H1 promotes tumorigenesis.

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hnRNP H1 and intronic G runs in the splicing control of the human rpL3 gene

Cited by 36 publications

References 34 publications

Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer

Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer

Human rpL3 induces G₁/S arrest or apoptosis by modulating p21^waf1/cip1 levels in a p53-independent manner

High-throughput analyses of hnRNP H1 dissects its multi-functional aspect

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hnRNP H1 and intronic G runs in the splicing control of the human rpL3 gene

Cited by 36 publications

References 34 publications

Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer

Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer

Human rpL3 induces G₁/S arrest or apoptosis by modulating p21waf1/cip1 levels in a p53-independent manner

High-throughput analyses of hnRNP H1 dissects its multi-functional aspect

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Human rpL3 induces G₁/S arrest or apoptosis by modulating p21^waf1/cip1 levels in a p53-independent manner