DDX39B promotes translation through regulation of pre-ribosomal RNA levels

Awasthi, Sharad; Chakrapani, Baskar; Mahesh, Arun; Chavali, Pavithra L.; Chavali, Sreenivas; Dhayalan, Arunkumar

doi:10.1080/15476286.2018.1517011

Cited by 24 publications

(18 citation statements)

References 33 publications

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“…We found that the RNA binding motif protein (RBM) family members (RBM5/6/25/33/39), SRRM1/2 and SRSF5/6/11, were in the central genes and played a role in the splicing and processing of mRNA. Moreover, two of the top 3 genes of intramodular connectivity (DDX39B and LUC7L) also serve important roles in alternative RNA splicing (Figure A and Table ) …”

Section: Resultsmentioning

confidence: 99%

Transcriptome analyses reveal molecular mechanisms underlying phenotypic differences among transcriptional subtypes of glioblastoma

Pan

Wang

Yang

et al. 2020

J Cellular Molecular Medi

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Using molecular signatures, previous studies have defined glioblastoma (GBM) subtypes with different phenotypes, such as the proneural (PN), neural (NL), mesenchymal (MES) and classical (CL) subtypes. However, the gene programmes underlying the phenotypes of these subtypes were less known. We applied weighted gene coexpression network analysis to establish gene modules corresponding to various subtypes. RNA-seq and immunohistochemical data were used to validate the expression of identified genes. We identified seven molecular subtype-specific modules and several candidate signature genes for different subtypes. Next, we revealed, for the first time, that radioresistant/chemoresistant gene signatures exist only in the PN subtype, as described by Verhaak et al, but do not exist in the PN subtype described by Phillips et al PN subtype. Moreover, we revealed that the tumour cells in the MES subtype GBMs are under ER stress and that angiogenesis and the immune inflammatory response are both significantly elevated in this subtype. The molecular basis of these biological processes was also uncovered. Genes associated with alternative RNA splicing are up-regulated in the CL subtype GBMs, and genes pertaining to energy synthesis are elevated in the NL subtype GBMs. In addition, we identified several survival-associated genes that positively correlated with glioma grades. The S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Pan Y-B, Wang S, Yang B, et al. Transcriptome analyses reveal molecular mechanisms underlying phenotypic differences among transcriptional subtypes of glioblastoma. J Cell Mol Med. 2020;24:3901-3916. https://doi.

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Section: Resultsmentioning

confidence: 99%

Transcriptome analyses reveal molecular mechanisms underlying phenotypic differences among transcriptional subtypes of glioblastoma

Pan

Wang

Yang

et al. 2020

J Cellular Molecular Medi

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“…Awasthi et al revealed that DDX39B was important for maintaining the normal levels of pre-ribosomal RNA by controlling its stability and synthesis. In addition, DDX39B was frequently upregulated in many cancer types and promoted the proliferative capacity of cells [21]. Activation of androgen receptor (AR) splice variants, especially AR-V7, are associated with unfavorable clinical outcome of prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of an alternative splicing-based prognostic signature for head and neck squamous cell carcinoma

Zhao¹,

Si²,

Li³

et al. 2020

J. Cancer

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Increasing evidence has demonstrated that changes in alternative splicing (AS) events are closely associated with the initiation and progression of cancer. However, the concrete role of AS in tumorigenesis of head and neck squamous cell carcinoma (HNSCC) is poorly known. In this study, we aimed to investigate the AS profile in HNSCC, and build up a robust AS-based prognostic signature for HNSCC. Our results revealed a total of 4068 overall survival (OS) associated AS events in the TCGA HNSCC cohort. The whole TCGA HNSCC cohort was randomly divided into discovery cohort and validation cohort. A prognostic signature including five AS events was developed with the discovery cohort based on the most significant OS-associated AS events. Then it was further successfully validated in the validation cohort. The AS-based risk signature was an independent prognostic indicator in both discovery cohort and validation cohort. This prognostic signature-based nomogram model showed excellent performance for predicting the OS of HNSCC. Splicing network analysis have identified the most correlated splicing factor-AS network in HNSCC. Collectively, we have constructed a robust AS-based prognostic signature which might contribute to improve the clinical outcome of HNSCC.

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“…JMJD6 is a histone demethylase that can demethylate histone H3 ( 43 ) and regulates nuclear factor κB (NF-κB) ( 44 ), both of which have been implicated in cocaine-associated plasticity ( 45 , 46 ). DDX39B is an RNA helicase that promotes translation through regulation of preribosomal RNA levels ( 47 ). mRNA expression of these genes matched INO80 binding patterns, and viral manipulation of INO80 affected these targets.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-proteasomal regulation of chromatin remodeler INO80 in the nucleus accumbens mediates persistent cocaine craving

et al. 2019

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Neuroadaptations in the nucleus accumbens (NAc) underlie cue-induced cocaine craving that intensifies (“incubates”) during abstinence and is believed to contribute to persistent relapse vulnerability. Changes in gene expression often govern perpetual behavioral abnormalities, but epigenetic plasticity during prolonged abstinence from drug exposure is poorly understood. We examined how E3 ubiquitin ligase TRIM3 dysregulates chromatin remodeler INO80 to mediate cocaine craving during prolonged abstinence. We found that INO80 expression increased in the NAc on abstinence day 30 (AD30) but not on AD1 following cocaine self-administration. Furthermore, TRIM3, which mediates degradation of INO80, was reduced on AD30, along with TRIM3-INO80 interaction. Viral-mediated gene transfer of INO80 or TRIM3 governed cocaine craving during prolonged abstinence. Lastly, chromatin immunoprecipitation followed by massively parallel DNA sequencing identified INO80-mediated transcriptional regulation of predicted pathways associated with cocaine plasticity. Together, these results demonstrate a novel ubiquitin-proteasomal-epigenetic mechanism by which TRIM3-INO80 mediates cocaine craving during prolonged abstinence.

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DDX39B promotes translation through regulation of pre-ribosomal RNA levels

Cited by 24 publications

References 33 publications

Transcriptome analyses reveal molecular mechanisms underlying phenotypic differences among transcriptional subtypes of glioblastoma

Transcriptome analyses reveal molecular mechanisms underlying phenotypic differences among transcriptional subtypes of glioblastoma

Identification and validation of an alternative splicing-based prognostic signature for head and neck squamous cell carcinoma

Ubiquitin-proteasomal regulation of chromatin remodeler INO80 in the nucleus accumbens mediates persistent cocaine craving

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