<i>PTBP1</i> mRNA isoforms and regulation of their translation

Tacca, Luisa M. Arake de; Pulos-Holmes, Mia C.; Floor, Stephen N.; Cate, J.H.D.

doi:10.1261/rna.070193.118

Cited by 26 publications

(15 citation statements)

References 53 publications

(68 reference statements)

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“…For instance, eIF3 was found to bind PTBP1 mRNA isoforms in a cell-cycle-dependent manner. A strong correlation could be established between eIF3 binding to PTBP1 mRNAs and repression of PTBP1 expression during the S phase of the cell cycle (65). The translation of several additional mRNAs is repressed by eIF3.…”

Section: Discussionmentioning

confidence: 93%

eIF3 interacts with histone H4 messenger RNA to regulate its translation

Hayek

Gross

Janvier

et al. 2021

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 93%

eIF3 interacts with histone H4 messenger RNA to regulate its translation

Hayek

Gross

Janvier

et al. 2021

Journal of Biological Chemistry

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“…In addition, we found three genes, COL5A1, COL1A2, and CP with lengthened 3′ UTR were upregulated in tumors in both the datasets. Several genes have been reported that their longer 3′ UTR isoform can enhance expression through trans -regulation mechanism ( Allen et al, 2013 ; Arake et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Comprehensive Analysis of APA Events and Their Association With Tumor Microenvironment in Lung Adenocarcinoma

et al. 2021

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BackgroundAlternative polyadenylation (APA) is a pervasive posttranscriptional mechanism regulating gene expression. However, the specific dysregulation of APA events and its potential biological or clinical significance in lung adenocarcinoma (LUAD) remain unclear.MethodsHere, we collected RNA-Seq data from two independent datasets: GSE40419 (n = 146) and The Cancer Genome Atlas (TCGA) LUAD (n = 542). The DaPars algorithm was employed to characterize the APA profiles in tumor and normal samples. Spearman correlation was used to assess the effects of APA regulators on 3′ UTR changes in tumors. The Cox proportional hazard model was used to identify clinically relevant APA events and regulators. We stratified 512 patients with LUAD in the TCGA cohort through consensus clustering based on the expression of APA factors.FindingsWe identified remarkably consistent alternative 3′ UTR isoforms between the two cohorts, most of which were shortened in LUAD. Our analyses further suggested that aberrant usage of proximal polyA sites resulted in escape from miRNA binding, thus increasing gene expression. Notably, we found that the 3′ UTR lengths of the mRNA transcriptome were correlated with the expression levels of APA factors. We further identified that CPSF2 and CPEB3 may serve as key regulators in both datasets. Finally, four LUAD subtypes according to different APA factor expression patterns displayed distinct clinical results and oncogenic features related to tumor microenvironment including immune, metabolic, and hypoxic status.InterpretationOur analyses characterize the APA profiles among patients with LUAD and identify two key regulators for APA events in LUAD, CPSF2 and CPEB3, which could serve as the potential prognostic genes in LUAD.

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“…3). Given the RNA stabilization function of hnRNP I/L [19,20,36,37] and their combination with UCA1 (Fig. 2), it is likely that hnRNP I/L may affect metabolism at least partially through increasing the UCA1 stability, which explains the similar metabolic pro les.…”

Section: Discussionmentioning

confidence: 98%

Long Noncoding RNA UCA1 Promotes Glutamine-Driven Anaplerosis of Bladder Cancer by Interacting With hnRNP I/L to Upregulate GPT2 Expression

Zhao¹,

Wu²,

X³

et al. 2020

Preprint

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Background: Glutamine-driven anaplerosis maintains the tricarboxylic acid (TCA) cycle by replenishing its carbon source of intermediates with the glutamine-derived carbons in cancer cells. Long noncoding RNA urothelial cancer associated 1 (UCA1), initially identified in bladder cancer, is associated with multiple cellular processes, including metabolic reprogramming. However, its characteristics in the anaplerosis context of bladder cancer (BLCA) remains elusive. Methods: The mechanism of UCA1 bound to and facilitated the combination of hnRNP I/L to the promoter of GPT2 gene was investigated by RNA pulldown, qRT-PCR, western blot, dual luciferase reporter assays, immunohistochemical staining, chromatin immunoprecipitation and chromatin isolation by RNA purification. Metabolomics analysis and metabolic flux analysis were conducted to assess the effects of UCA1, hnRNP I/L, and GPT2 on metabolic reprogramming of BLCA.Results: We identified UCA1 as a binding partner of heterogeneous nuclear ribonucleoproteins (hnRNPs) I and L, RNA-binding proteins with no previously known role in metabolic reprogramming. UCA1 and hnRNP I/L profoundly affected glycolysis, TCA cycle, glutaminolysis, and viability of BLCA cells. Importantly, UCA1 specifically bound to and facilitated the combination of hnRNP I/L to the promoter of glutamic pyruvate transaminase 2 (GPT2) gene, resulting in upregulated expression of GPT2 and enhanced glutamine-derived carbons in the TCA cycle. We also systematically confirmed the influence of UCA1, hnRNP I/L, and GPT2 on metabolism and proliferation via glutamine-driven anaplerosis in BLCA cells. Conclusions: Our study reveals the critical mechanism by which UCA1 forms a functional UCA1-hnRNP I/L complex that upregulates GPT2 expression to promote glutamine-driven TCA cycle anaplerosis, providing novel evidence that lncRNA regulates metabolic reprogramming in tumor cells.

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PTBP1 mRNA isoforms and regulation of their translation

Cited by 26 publications

References 53 publications

eIF3 interacts with histone H4 messenger RNA to regulate its translation

eIF3 interacts with histone H4 messenger RNA to regulate its translation

Comprehensive Analysis of APA Events and Their Association With Tumor Microenvironment in Lung Adenocarcinoma

Long Noncoding RNA UCA1 Promotes Glutamine-Driven Anaplerosis of Bladder Cancer by Interacting With hnRNP I/L to Upregulate GPT2 Expression

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