scholarly journals Targeting Splicing Factor SRSF6 for Cancer Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Wenting She ◽  
Jun Shao ◽  
Rong Jia
Keyword(s):  
Alternative Splicing ◽  
Protein Structure ◽  
Cancer Therapy ◽  
Potential Application ◽  
Target Genes ◽  
Splicing Factor ◽  
Regulatory Mechanisms ◽  
The Past ◽  
Oncogenic Gene ◽  
Gene Mrna

Aberrant alternative splicing of pre-mRNA is an emerging cancer hallmark. Many cancer-associated genes undergo alternative splicing to produce multiple isoforms with diverse or even antagonistic functions. Oncogenic isoforms are often up-regulated, whereas tumor suppressive isoforms are down-regulated during tumorigenesis. Serine/arginine-rich splicing factor 6 (SRSF6) is an important splicing factor that regulates the alternative splicing of hundreds of target genes, including many cancer-associated genes. The potential roles of SRSF6 in cancers have attracted increasing attentions in the past decade. Accumulated pieces of evidence have shown that SRSF6 is a potential oncogenic gene that promotes oncogenic splicing when overexpressed. Targeting SRSF6 may suppress tumorigenesis. In this review, we describe the gene, mRNA, and protein structure of SRSF6; summarize the current understanding of the expression, functions, and regulatory mechanisms of SRSF6 during tumorigenesis; and discuss the potential application of targeting SRSF6 in cancer treatment.

scholarly journals Inhibition of a transcriptional repressor rescues hearing in a splicing factor–deficient mouse

2020 ◽  
Vol 3 (12) ◽  
pp. e202000841
Author(s):  
Yoko Nakano ◽  
Susan Wiechert ◽  
Bernd Fritzsch ◽  
Botond Bánfi
Keyword(s):  
Alternative Splicing ◽  
Target Genes ◽  
Transcriptional Repressor ◽  
Dominant Negative ◽  
Splicing Factor ◽  
Loss Of Function ◽  
Transgenic Expression ◽  
Mechanosensory Hair Cells

In mechanosensory hair cells (HCs) of the ear, the transcriptional repressor REST is continuously inactivated by alternative splicing of its pre-mRNA. This mechanism of REST inactivation is crucial for hearing in humans and mice. Rest is one of many pre-mRNAs whose alternative splicing is regulated by the splicing factor SRRM4; Srrm4 loss-of-function mutation in mice (Srrm4bv/bv) causes deafness, balance defects, and degeneration of all HC types other than the outer HCs (OHCs). The specific splicing alterations that drive HC degeneration in Srrm4bv/bv mice are unknown, and the mechanism underlying SRRM4-independent survival of OHCs is undefined. Here, we show that transgenic expression of a dominant-negative REST fragment in Srrm4bv/bv mice is sufficient for long-term rescue of hearing, balancing, HCs, alternative splicing of Rest, and expression of REST target genes including the Srrm4 paralog Srrm3. We also show that in HCs, SRRM3 regulates many of the same exons as SRRM4; OHCs are unique among HCs in that they transiently down-regulate Rest transcription as they mature to express Srrm3 independently of SRRM4; and simultaneous SRRM4–SRRM3 deficiency causes complete HC loss by preventing inactivation of REST in all HCs. Thus, our data reveal that REST inactivation is the primary and essential role of SRRM4 in the ear, and that OHCs differ from other HCs in the SRRM4-independent expression of the functionally SRRM4-like splicing factor SRRM3.

scholarly journals Phosphorylation status of the Kep1 protein alters its affinity for its protein binding partner alternative splicing factor ASF/SF2

2006 ◽  
Vol 400 (1) ◽  
pp. 91-97 ◽  
Author(s):  
Cécile Robard ◽  
Alex Daviau ◽  
Marco Di Fruscio
Keyword(s):  
Alternative Splicing ◽  
Protein Binding ◽  
Cell Line ◽  
Topoisomerase I ◽  
Target Genes ◽  
Rna Binding ◽  
Splicing Factor ◽  
Alternatively Spliced ◽  
Alternative Splicing Factor

Mutations in the Drosophila kep1 gene, encoding a single maxi KH (K homology) domain-containing RNA-binding protein, result in a reduction of fertility in part due to the disruption of the apoptotic programme during oogenesis. This disruption is concomitant with the appearance of an alternatively spliced mRNA isoform encoding the inactive caspase dredd. We generated a Kep1 antibody and have found that the Kep1 protein is present in the nuclei of both the follicle and nurse cells during all stages of Drosophila oogenesis. We have shown that the Kep1 protein is phosphorylated in ovaries induced to undergo apoptosis following treatment with the topoisomerase I inhibitor camptothecin. We have also found that the Kep1 protein interacts specifically with the SR (serine/arginine-rich) protein family member ASF/SF2 (alternative splicing factor/splicing factor 2). This interaction is independent of the ability of Kep1 to bind RNA, but is dependent on the phosphorylation of the Kep1 protein, with the interaction between Kep1 and ASF/SF2 increasing in the presence of activated Src. Using a CD44v5 alternative splicing reporter construct, we observed 99% inclusion of the alternatively spliced exon 5 following kep1 transfection in a cell line that constitutively expresses activated Src. This modulation in splicing was not observed in the parental NIH 3T3 cell line in which we obtained 7.5% exon 5 inclusion following kep1 transfection. Our data suggest a mechanism of action in which the in vivo phosphorylation status of the Kep1 protein affects its affinity towards its protein binding partners and in turn may allow for the modulation of alternative splice site selection in Kep1–ASF/SF2-dependent target genes.

An exon-centric perspective1Canadian Society of Molecular Biosciences (CSMB) Senior Investigator Award

2012 ◽  
Vol 90 (5) ◽  
pp. 603-612 ◽  
Author(s):  
Benjamin J. Blencowe
Keyword(s):  
Alternative Splicing ◽  
Computational Methods ◽  
Large Datasets ◽  
Regulatory Mechanisms ◽  
The Past ◽  
Human Genes ◽  
Insight Into ◽  
Remarkable Progress ◽  
Discrete Networks ◽  
Made In

During the past ten years, remarkable progress has been made in our understanding of the complexity and regulation of alternative splicing. The generation of large datasets of quantitative alternative splicing profiling information has revealed that transcripts from at least 95% of multi-exon human genes undergo alternative splicing, and that thousands of exons in mammalian transcriptomes are subject to striking regulatory patterns. Together with advanced computational methods, these datasets have enabled the inference of a predictive code for tissue-dependent alternative splicing. This code has further provided new insight into splicing regulatory mechanisms. Collectively, these approaches are revealing the existence of discrete networks of exons that are coordinately regulated in diverse biologically normal and disease contexts. A major challenge ahead is to systematically determine the functions of exons comprising these exon networks as well as the factors and mechanisms responsible for their regulation. This perspective provides an account of progress in these areas and also discusses future avenues of exon-centric exploration.

Bi19S27I3 nanorods: a new candidate for photothermal therapy in the first and second biological near-infrared windows

Nanoscale ◽  
2021 ◽  
Author(s):  
Jinsong Xiong ◽  
Qinghuan Bian ◽  
Shuijin Lei ◽  
Yatian Deng ◽  
Kehan Zhao ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Photothermal Therapy ◽  
Near Infrared ◽  
Research Interest ◽  
The Past ◽  
Nir Light ◽  
Considerable Research ◽  
Key Factor

Near-infrared (NIR) light induced photothermal cancer therapy using nanomaterials as photothermal agents has attracted considerable research interest over the past few years. As the key factor in the photothermal therapy...

scholarly journals Alternative splicing landscapes in Arabidopsis thaliana across tissues and stress conditions highlight major functional differences with animals

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Guiomar Martín ◽  
Yamile Márquez ◽  
Federica Mantica ◽  
Paula Duque ◽  
Manuel Irimia
Keyword(s):  
Gene Expression ◽  
Arabidopsis Thaliana ◽  
Alternative Splicing ◽  
Stress Responses ◽  
Target Genes ◽  
Intron Retention ◽  
Single Gene ◽  
Exon Skipping ◽  
Environmental Response ◽  
Biotic Stresses

Abstract Background Alternative splicing (AS) is a widespread regulatory mechanism in multicellular organisms. Numerous transcriptomic and single-gene studies in plants have investigated AS in response to specific conditions, especially environmental stress, unveiling substantial amounts of intron retention that modulate gene expression. However, a comprehensive study contrasting stress-response and tissue-specific AS patterns and directly comparing them with those of animal models is still missing. Results We generate a massive resource for Arabidopsis thaliana, PastDB, comprising AS and gene expression quantifications across tissues, development and environmental conditions, including abiotic and biotic stresses. Harmonized analysis of these datasets reveals that A. thaliana shows high levels of AS, similar to fruitflies, and that, compared to animals, disproportionately uses AS for stress responses. We identify core sets of genes regulated specifically by either AS or transcription upon stresses or among tissues, a regulatory specialization that is tightly mirrored by the genomic features of these genes. Unexpectedly, non-intron retention events, including exon skipping, are overrepresented across regulated AS sets in A. thaliana, being also largely involved in modulating gene expression through NMD and uORF inclusion. Conclusions Non-intron retention events have likely been functionally underrated in plants. AS constitutes a distinct regulatory layer controlling gene expression upon internal and external stimuli whose target genes and master regulators are hardwired at the genomic level to specifically undergo post-transcriptional regulation. Given the higher relevance of AS in the response to different stresses when compared to animals, this molecular hardwiring is likely required for a proper environmental response in A. thaliana.

scholarly journals Potential application of gold nanoparticles in food packaging: a mini review

Gold Bulletin ◽  
2021 ◽  
Author(s):  
Saeed Paidari ◽  
Salam Adnan Ibrahim
Keyword(s):  
Gold Nanoparticles ◽  
Potential Application ◽  
Food Industry ◽  
Food Packaging ◽  
Industrial Applications ◽  
Mechanisms Of Action ◽  
Microbial Load ◽  
Food Sector ◽  
The Past ◽  
Industry Applications

AbstractIn the past few decades, there have been remarkable advances in our knowledge of gold nanoparticles (AuNPs) and synthesizing methods. AuNPs have become increasingly important in biomedical and industrial applications. As a newly implemented method, AuNPs are being used in nanopackaging industries for their therapeutic and antibacterial characteristics as well as their inert and nontoxic nature. As with other NPs, AuNPs have privileges and disadvantages when utilized in the food sector, yet a significant body of research has shown that, due to the specific nontoxic characteristics, AuNPs could be used to address other NP flaws. In this mini review, we present synthesizing methods, food industry applications, and mechanisms of action of gold nanoparticles. Regarding the investigations, gold nanoparticles can play a major role to reduce microbial load in foodstuff and therefore can be implemented in food packaging as an effective approach.

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