Analysis of RNA Processing Mediated by LLPS in Cancers

Cancer is caused by genetic alterations that typically reprogram gene transcription and sometimes RNA splicing. Studies have shown that liquid-liquid phase separation (LLPS) is associated with the spatiotemporal regulation of gene expression. Aggregation or condensation of splicing regulatory factors mediates RNA splicing activation and may expand its gene regulatory capacity in mammals. AKAP95 is a nuclear member of the A-kinase anchoring protein family, with multiple activities. AKAP95 integrates the regulation of transcription and RNA splicing, and binds many factors in RNA processing and transcription. AKAP95 directly regulates splicing of a minigene reporter, and modulates alternative splicing AKAP95 directly regulates splicing of a minigene reporter, and modulates alternative splicing of the human transcriptome by directly binding to pre-mRNA introns in a ZF-dependent manner. However, the fundamental molecular properties underlying its activity in gene regulation are unclear.

Fig. 1. A model for how AKAP95 condensates may regulate gene expression for tumorigenesis. (Li W, et al., 2020)

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AKAP95 is a nuclear protein that integrates transcriptional and pre-mRNA splicing regulation, and recent studies have shown that AKAP95 undergoes intrinsically disordered protein (IDR)-mediated LLPS, which is critical for its activities in regulating splicing and supporting tumorigenesis. Our experts are commmitted to characterizing the fundamental molecular properties of AKAP95 in regulating gene expression and cancer, trying to explain the role of AKAP95 in supporting tumorigenesis using LLPS, and developing possible strategies to suppress cancer by disrupting or hardening AKAP95.

CD BioSciences offers specialized services to analyze LLPS-mediated regulation of RNA processing in cancer. In collaboration with cancer researchers, cell biologists and biophysicists, we offer cutting-edge technologies to analyze RNA processing-related condensates in cancer, as shown below. If you would like to analyze other RNA processing-related condensates in cancer, you can contact us directly for a customized service.

• AKAP95 (Ovarian and colorectal cancer)
• YBX1 (Sarcoma)
• SNHG9(Breast cancer)
• YTHDC1 (Acute myeloid leukemia)

We offer a comprehensive model of the role of AKAP95 phase segregation in the spatial regulation of gene expression underlying tumorigenesis. Our lab has a sophisticated cellular, in vivo, computer, and bioinformatics one-stop platform to help our clients analyze the biochemical activity of AKAP95 condensates in gene regulation, and link their biophysical properties to their physiological functions in tumorigenesis. Intriguingly, our technical team is commmitted to developing AKAP95-mediated phase separation as an effective therapeutic strategy for the treatment of drug-resistant cancers.

• Design YS or YA mutations result in complete inactivation of AKAP95.
• Sclerotic AKAP95 condensates slow down the internal biochemical reaction kinetics by limiting the movement and interactions of other macromolecules such as other splicing regulators and RNA substrates.

Combining proteomics, transcriptomics, imaging, genetics, epidemiology and computer data, CD BioSciences aims to analyze the ability of AKAP95 condensates to regulate gene expression and support tumorigenesis, to help our clients develop therapeutic targets for cancer treatment. Our services are widely used in preclinical research in cancer biology, diagnosis and treatment. If you are interested in our services, please feel free to contact us.