Heterogeneous Nuclear Ribonucleoproteins Involved in the Functioning of Telomeres in Malignant Cells

Shishkin, S. S.; Ковалев, Л. И.; Pashintseva, Natalya; Kovaleva, M. A.; Lisitskaya, K. V.

doi:10.3390/ijms20030745

Cited by 27 publications

(24 citation statements)

References 211 publications

(403 reference statements)

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“…HNRNPA3 is part of the hnRNP A/B family. The proteins in this family are characterized by two tandem RNA recognition motifs (RRMs) in the N-terminal region 45 , 46 . Systematic analysis of their Drosophila homologs indicates that these hnRNP A/B proteins control overlapping but diverse targets in pre-mRNA processing 47 .…”

Section: Resultsmentioning

confidence: 99%

Epidermal progenitors suppress GRHL3-mediated differentiation through intronic polyadenylation promoted by CPSF-HNRNPA3 collaboration

et al. 2021

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In self-renewing somatic tissue such as skin epidermis, terminal differentiation genes must be suppressed in progenitors to sustain regenerative capacity. Here we show that hundreds of intronic polyadenylation (IpA) sites are differentially used during keratinocyte differentiation, which is accompanied by downregulation of the Cleavage and Polyadenylation Specificity Factor (CPSF) complex. Sustained CPSF expression in undifferentiated keratinocytes requires the contribution from the transcription factor MYC. In keratinocytes cultured in undifferentiation condition, CSPF knockdown induces premature differentiation and partially affects dynamically used IpA sites. These sites include an IpA site located in the first intron of the differentiation activator GRHL3. CRISPR knockout of GRHL3 IpA increased full-length GRHL3 mRNA expression. Using a targeted genetic screen, we identify that HNRNPA3 interacts with CPSF and enhances GRHL3 IpA. Our data suggest a model where the interaction between CPSF and RNA-binding proteins, such as HNRNPA3, promotes site-specific IpA and suppresses premature differentiation in progenitors.

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Section: Resultsmentioning

confidence: 99%

Epidermal progenitors suppress GRHL3-mediated differentiation through intronic polyadenylation promoted by CPSF-HNRNPA3 collaboration

et al. 2021

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“…7,8 As the most critical alternative splicing regulator, heterogeneous nuclear ribonucleoproteins (hnRNPs) family are responsible for the maturation of pre-mRNAs into functional mRNAs as well as the stabilization of mRNA translocation. 9,10 Through the RNA binding domains (RBDs), hnRNPs accomplish the recognition of specific RNA sequences and control various biological processes of RNA function and metabolism. 11,12 Mechanistically, hnRNPs constitute mRNA-protein 40S core complex via binding to RNA elements including exon and intron splicing regulators, which precisely control the alternative splicing of pre-mRNAs.…”

Section: Introductionmentioning

confidence: 99%

“…As the most critical alternative splicing regulator, heterogeneous nuclear ribonucleoproteins (hnRNPs) family are responsible for the maturation of pre‐mRNAs into functional mRNAs as well as the stabilization of mRNA translocation 9,10 . Through the RNA binding domains (RBDs), hnRNPs accomplish the recognition of specific RNA sequences and control various biological processes of RNA function and metabolism 11,12 .…”

Section: Introductionmentioning

confidence: 99%

Pan‐cancer analysis of alternative splicing regulator heterogeneous nuclear ribonucleoproteins (hnRNPs) family and their prognostic potential

Liu

Shen

et al. 2020

J Cellular Molecular Medi

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“…In our study, the mRBPs HnRNPA1 and HnRNPA2B were found as downregulated SDEG in COPD and this profile was predicted by IPA to inhibit telomere extension by telomerase. Early studies established that hnRNP-A1, hnRNP-A2, and hnRNP-B1 proteins can interact with telomeres and are products of two different genes (HNRNPA1 and HNRNPA2B1) but display similar structures (two RRMs and four RGG motifs in each) (95). The mRBP hnRNP A1 is the best characterized and found to be associated with human telomeres in vivo (96); depletion of hnRNP A/B proteins in human embryonic kidney 293 cell extracts greatly reduced telomerase activity, which was rescued by addition of recombinant hnRNP A1 (96).…”

Section: Discussionmentioning

confidence: 99%

Posttranscriptional Gene Regulatory Networks in Chronic Airway Inflammatory Diseases: In silico Mapping of RNA-Binding Protein Expression in Airway Epithelium

et al. 2020

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Background: Posttranscriptional gene regulation (PTGR) contributes to inflammation through alterations in messenger RNA (mRNA) turnover and translation rates. RNA-binding proteins (RBPs) coordinate these processes but their role in lung inflammatory diseases is ill-defined. We evaluated the expression of a curated list of mRNA-binding RBPs (mRBPs) in selected Gene Expression Omnibus (GEO) transcriptomic databases of airway epithelium isolated from chronic obstructive pulmonary disease (COPD), severe asthma (SA) and matched control subjects, hypothesizing that global changes in mRBPs expression could be used to infer their pathogenetic roles and identify novel disease-related regulatory networks. Methods: A published list of 692 mRBPs [Nat Rev Genet 2014] was searched in GEO datasets originated from bronchial brushings of stable COPD patients (C), smokers (S), non-smokers (NS) controls with normal lung function (n = 6/12/12) (GEO ID: GSE5058) and of (SA) and healthy control (HC) (n = 6/12) (GSE63142). Fluorescence intensity data were extracted and normalized on the medians for fold change (FC) comparisons. FCs were set at ≥ |1.5| with a false discovery rate (FDR) of ≤ 0.05. Pearson correlation maps and heatmaps were generated using tMEV tools v4_9_0.45. DNA sequence motifs were searched using PScan-ChIP. Gene Ontology (GO) was performed with Ingenuity Pathway Analysis (IPA) tool. Results: Significant mRBP expression changes were detected for S/NS, COPD/NS and COPD/S (n = 41, 391, 382, respectively). Of those, 32% of genes changed by FC ≥ |1.5| in S/NS but more than 60% in COPD/NS and COPD/S (n = 13, 267, 257, respectively). Genes were predominantly downregulated in COPD/NS (n = 194, 73%) and COPD/S (n = 202, 79%), less so in S/NS (n = 4, 31%). Unsupervised cluster analysis identified in 4 out of 12 S the same mRBP pattern seen in C, postulating subclinical COPD. Significant DNA motifs enrichment for transcriptional regulation Ricciardi et al. Airway Epithelial RNA-Binding Protein Profiling was found for downregulated RBPs. Correlation analysis identified five clusters of co-expressed mRBPs. GO analysis revealed significant enrichments in canonical pathways both specific and shared among comparisons. Unexpectedly, no significant mRBPs modulation was found in SA compared to controls. Conclusions: Airway epithelial mRBPs profiling reveals a COPD-specific global downregulation of RBPs shared by a subset of control smokers, the potential of functional cooperation by coexpressed RBPs and significant impact on relevant pathogenetic pathways in COPD. Elucidation of PTGR in COPD could identify disease biomarkers or pathways for therapeutic targeting.

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Heterogeneous Nuclear Ribonucleoproteins Involved in the Functioning of Telomeres in Malignant Cells

Cited by 27 publications

References 211 publications

Epidermal progenitors suppress GRHL3-mediated differentiation through intronic polyadenylation promoted by CPSF-HNRNPA3 collaboration

Epidermal progenitors suppress GRHL3-mediated differentiation through intronic polyadenylation promoted by CPSF-HNRNPA3 collaboration

Pan‐cancer analysis of alternative splicing regulator heterogeneous nuclear ribonucleoproteins (hnRNPs) family and their prognostic potential

Posttranscriptional Gene Regulatory Networks in Chronic Airway Inflammatory Diseases: In silico Mapping of RNA-Binding Protein Expression in Airway Epithelium

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