Modulation of alternative splicing by anticancer drugs

Rehman, Sufia; Husain, Mohammed Amir; Sarwar, Tarique; Ishqi, Hassan Mubarak; Tabish, Mohammad

doi:10.1002/wrna.1283

Cited by 17 publications

(6 citation statements)

References 78 publications

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“…The second example is the mechanism of the actions of cisplatin and gemcitabine [23]. Two CASP9-encoded protein isoforms, CASP9a and CASP9b, have different effects on apoptosis.…”

Section: Resultsmentioning

confidence: 99%

CODA-ML: context-specific biological knowledge representation for systemic physiology analysis

et al. 2019

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Background Computational analysis of complex diseases involving multiple organs requires the integration of multiple different models into a unified model. Different models are often constructed in heterogeneous formats. Thus, the integration of the models requires a standard language format that can effectively represent essential biological information. However, the previously introduced formats have limitations that prevent from adequately representing essential biological information, particularly specifications of bio-molecules and biological contexts. Results We defined an XML-based markup language called context-oriented directed association markup language (CODA-ML), which better represents essential biological information. The CODA-ML has two major strengths in designating molecular specifications and biological contexts. It can cover heterogeneous entity types involved in biological events (e.g. gene/protein, compound, cellular function, disease). Molecular types of entities can have molecular specifications which include detailed information of a molecule from isoforms to modifications, enabling high-resolution representation of molecules. In addition, it can distinguish biological events that vary depending on different biological contexts such as cell types or disease conditions. Especially representation of inter-cellular events as well as intra-cellular events is available. These two major strengths can resolve contradictory associations when different models are integrated into one unified model, which improves the accuracy of the model. Conclusions With the CODA-ML, diverse models such as signaling pathways, metabolic pathways, and gene regulatory pathways can be represented in a unified language format. Heterogeneous entity types can be covered by the CODA-ML, thus it enables detailed description for the mechanisms of diseases or drugs from multiple perspectives (e.g., molecule, function or disease). The CODA-ML is expected to help integrate different models into one systemic model in an efficient and effective. The unified model can be used to perform computational analysis not only for cancer but also for other complex diseases involving multiple organs beyond a single cell. Electronic supplementary material The online version of this article (10.1186/s12859-019-2812-7) contains supplementary material, which is available to authorized users.

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“…The second example is the mechanism of the actions of cisplatin and gemcitabine [23]. Two CASP9-encoded protein isoforms, CASP9a and CASP9b, have different effects on apoptosis.…”

Section: Resultsmentioning

confidence: 99%

CODA-ML: context-specific biological knowledge representation for systemic physiology analysis

et al. 2019

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“…Arnt variants itself being transcription factors can directly control the regulation of many important genes involved in cancer and diabetes. An exciting possibility raised by this study is that the effectiveness of anti‐cancer and anti‐diabetic therapies may be enhanced by clinical drugs, natural products, and their synthesized analogs that target alternative splicing machinery . Some alternative splicing related databases and web servers may also be helpful to improve the alternative splicing therapy for treating cancer, diabetes and other disease.…”

Section: Resultsmentioning

confidence: 99%

Identification of differentially expressed three novel transcript variants of mouse ARNT gene

et al. 2015

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The aryl hydrocarbon receptor nuclear translocator (ARNT/ HIF1-b) is an obligatory transcriptional partner of the aryl hydrocarbon receptor (AHR) and hypoxia-inducible factor-1a (HIF-1a). It has a basic helix-loop-helix domain that belongs to period-ARNT-single-minded (PAS) protein family. PAS proteins act as heterodimeric transcription factors with ARNT being master dimerization partner. The ARNT-HIF-1a complex is an important transcriptional regulator of the hypoxic response of the tumor cells. Previous studies have reported two transcript variants of the gene produced by alternative splicing in mouse. One transcript variant contains all 22 exons while the other variant lacks exon-E5. In our study, using combinatorial approach comprising bioinformatics tools and molecular biology techniques involving RT-PCR, semi-nested PCR, sequencing and qPCR, we have identified three novel transcript variants of Arnt gene in mouse. All three new transcripts arise as a result of alternative splicing of newly identified exons with exon-E2, replacing reported exon-E1. These transcripts encode for three protein isofoms having different N-termini. The expression of these transcripts was found to be different in different tissues of adult mice. In silico analysis of the upstream region of the new exons revealed three distinct promoter regions designated as PA, PB and PC present upstream of newly identified exons. These promoters possess potential signature sequences for common as well as different transcription factors suggesting complex regulation of Arnt gene. In silico post translational studies of the conceptually translated amino acid sequences of these transcripts show similarity in some of the properties while differ in others. The diversity at N-termini of protein isoforms suggests the possibility of forming different complexes in different tissues and may also be important for unique interactions with partner molecules. V C 2015 IUBMB Life, 68(2): [122][123][124][125][126][127][128][129][130][131][132][133][134][135] 2016

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“…Changes in mRNA structure by alternative splicing may lead to changes in the function of a protein such as alteration in protein stability, intracellular localization and binding property apart from others. In some cases, alternative splicing generates isoforms having opposite functions . It is also known that the regulation of expression of genes through alternative splicing is more versatile as compared to the regulation through promoter activity .…”

Section: Introductionmentioning

confidence: 99%

“…In some cases, alternative splicing generates isoforms having opposite functions . It is also known that the regulation of expression of genes through alternative splicing is more versatile as compared to the regulation through promoter activity . It is therefore important to study the existence of alternatively spliced isoforms and their cellular functions.…”

Section: Introductionmentioning

confidence: 99%

Identification of two novel isoforms of mouse NUR77 lacking N‐terminal domains

et al. 2017

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Nur77 is a member of nuclear receptor superfamily that acts as a transcription factor and regulates expression of multiple genes. Subcellular localization of Nur77 protein plays an important role in the survival and cell death. In this study, we have predicted and confirmed alternatively spliced two new transcripts of Nur77 gene in mouse. The newly identified transcripts have their alternatively spliced first exon located upstream of published 5'-UTR of the gene. Transcription factor binding sites in the possible promoter regions of these transcripts were also analyzed. Expression of novel transcript variants was found to be significantly lower than the already published transcript. New transcript variants encode for NUR77 protein isoforms which are significantly smaller in size due to lack of transactivation domain and a part of DNA binding domain. Western blot analysis using NUR77 specific antibody confirmed the existence of these smaller variants in mouse. Localization of these new isoforms was predicted to be majorly outside the nucleus. In silico analysis of the conceptually translated proteins was performed using different bioinformatics tools. The results obtained in this study offer further insight into novel area of research on extensively studied Nur77. © 2017 IUBMB Life, 69(2):106-114, 2017.

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Modulation of alternative splicing by anticancer drugs

Cited by 17 publications

References 78 publications

CODA-ML: context-specific biological knowledge representation for systemic physiology analysis

CODA-ML: context-specific biological knowledge representation for systemic physiology analysis

Identification of differentially expressed three novel transcript variants of mouse ARNT gene

Identification of two novel isoforms of mouse NUR77 lacking N‐terminal domains

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