Splicing factor hnRNPH drives an oncogenic splicing switch in gliomas

LeFave, Clare V.; Squatrito, Massimo; Vorlová, Sandra; Rocco, Gina L.; Brennan, Cameron; Holland, Eric C.; Pan, Ying Xian; Cartegni, Luca

doi:10.1038/emboj.2011.259

Cited by 138 publications

(153 citation statements)

References 67 publications

(85 reference statements)

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“…38 Future efforts to develop treatments targeting these diseases will rely on an understanding of the binding mechanisms of the protein. We have confirmed the strong presence of G-rich tracts around hnRNP H1 interactions sites.…”

Section: Resultsmentioning

confidence: 99%

“…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. 2 Our data, however, is supportive of the TGGG tetramer as a prevalent component of the hnRNP H1 binding motif, with particular enrichment in intronic regions.…”

Section: Binding Site Characteristicsmentioning

confidence: 99%

“…Both pathways are highly linked to tumorigenesis, agreeing with the described role for hnRNP H1 in glioma. 15 The MAPK pathway encompasses key signaling components and phosphorylation events that transmit extracellular signals modulating cell growth, differentiation, proliferation, apoptosis and migration. Targeting MAPK signaling is currently being tested as a cancer treatment (reviewed in 34 ).…”

Section: Binding Site Characteristicsmentioning

confidence: 99%

“…13 High levels of hnRNP H1 have been linked also to glioblastoma development via increased expression of a Raf isoform (A-Raf) which results in apoptosis inhibition. 14 Other studies have linked hnRNP H1-mediated exon skipping of the RON mRNA to tumor migration and invasion, 15 and similarly hnRNP H1 activity has been shown to regulate the splicing of the IG20 mRNA, shifting the balance between the pro-apoptotic isoform (IG20) and the anti-apoptotic isoform (MADD/ DENN) in glioblastoma cells. 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.…”

Section: Introductionmentioning

confidence: 99%

“…14 Other studies have linked hnRNP H1-mediated exon skipping of the RON mRNA to tumor migration and invasion, 15 and similarly hnRNP H1 activity has been shown to regulate the splicing of the IG20 mRNA, shifting the balance between the pro-apoptotic isoform (IG20) and the anti-apoptotic isoform (MADD/ DENN) in glioblastoma cells. 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).…”

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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Section: Resultsmentioning

confidence: 99%

Section: Binding Site Characteristicsmentioning

confidence: 99%

Section: Binding Site Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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RNA m⁶Amethylation in cancer

et al. 2022

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N 6 -methyladenosine (m 6 A) is one of the most abundant internal modifications in eukaryotic messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs). It is a reversible and dynamic RNA modification that has been observed in both internal coding segments and untranslated regions. Studies indicate that m 6 A modifications play important roles in translation, RNA splicing, export, degradation and ncRNA processing control. In this review, we focus on the profiles and biological functions of RNA m 6 A methylation on both mRNAs and ncRNAs. The dynamic modification of m 6 A and its potential roles in cancer development are discussed. Moreover, we discuss the possibility of m 6 A modifications serving as potential biomarkers for cancer diagnosis and targets for therapy.RNAs including messenger RNA (mRNA) and noncoding RNA (ncRNA). The N6 position of adenosine can be reversibly methylated and unmethylated by 'm 6 A writer' and 'm 6 A eraser' proteins, respectively, and m 6 A RNA can be recognized and bound by 'm 6 A reader' proteins [2] (Fig. 1, Table 1, Box 1).

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Splicing factor poly(rC)‐binding protein 1 is a novel and distinctive tumor suppressor

Guo

Jia

2018

Journal Cellular Physiology

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A lot of evidence has been found on the link between tumorigenesis and the aberrant expression of splicing factors. A number of splicing factors have been reported to be either oncogenic or overexpressed in cancer cells. However, splicing factors can also play negative roles in tumorigenesis. In the current review, we focus on splicing factor poly(rC)-binding protein 1 (PCBP1), a novel tumor suppressor that is characterized by downregulation in many cancer types and shows inhibition of tumor formation and metastasis. Notably, the messenger RNA levels of PCBP1 are not significantly decreased in most cancer types. In fact, PCBP1 protein is often degraded or shows a loss-of-function through phosphorylation in cancer cells. PCBP1 is highly homologous to its family member, PCBP2. Interestingly, PCBP2 appears to be an oncogenic splicing factor. A growing body of evidence has shown that PCBP1 regulates alternative splicing, translation, and RNA stability of many cancer-related genes. Taking together, PCBP1 has distinctive tumor suppressive functions, and increasing PCBP1 expression may represent a new approach for cancer treatment.

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Splicing factor hnRNPH drives an oncogenic splicing switch in gliomas

Cited by 138 publications

References 67 publications

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

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

RNA m⁶Amethylation in cancer

Splicing factor poly(rC)‐binding protein 1 is a novel and distinctive tumor suppressor

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Splicing factor hnRNPH drives an oncogenic splicing switch in gliomas

Cited by 138 publications

References 67 publications

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

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

RNA m6Amethylation in cancer

Splicing factor poly(rC)‐binding protein 1 is a novel and distinctive tumor suppressor

Contact Info

Product

Resources

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RNA m⁶Amethylation in cancer