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Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
Published on: December 26, 2016
Functional screens identify coordinators of RNA molecule birth, life, and death as targetable cancer vulnerabilities
Christian J Braun1, Michael T Hemann2
1Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.
Abstract:
RNA molecules are subject to a complex co-transcriptional and post-transcriptional life cycle, controlled at all stages by RNA binding proteins (RBPs) and non-coding RNAs that influence mRNA stability, splicing, localization, and decay. Together with mechanisms regulating the process of transcription itself, non-coding RNAs and RBPs contribute to a model of para-transcriptional coordination of gene expression, which is utilized during normal tissue physiology and cancer development in order to execute complex gene expression programs. Several key regulators of RNA biology, such as certain splice factors, represent bona fide cancer vulnerabilities, but our understanding of these processes is still far away from being comprehensive. Genetic forward screens utilizing technologies such as transposons, RNAi and CRISPR aid the field in rapidly establishing functional phenotypes and genetic cancer cell addictions. This review focuses on four individual regulatory gene expression processes governed by regulators of the RNA life cycle, the impact of functional genomics on streamlining the discovery process and the role of such mechanisms in tumor biology.
Insights
RNA binding proteins (RBPs) and non-coding RNAs regulate gene expression throughout the RNA lifecycle. Understanding these RNA regulators is crucial for cancer biology and developing new therapies.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Biology
Background:
- RNA molecules undergo complex co-transcriptional and post-transcriptional regulation.
- RNA binding proteins (RBPs) and non-coding RNAs influence mRNA stability, splicing, localization, and decay.
- These RNA regulators are integral to gene expression programs in normal physiology and cancer.
Purpose of the Study:
- To review key regulatory gene expression processes governed by RNA lifecycle regulators.
- To highlight the impact of functional genomics on accelerating discovery in this field.
- To discuss the role of RNA regulatory mechanisms in tumor biology.
Main Methods:
- Review of current literature on RNA biology and cancer.
- Focus on functional genomics approaches (transposons, RNAi, CRISPR).
- Analysis of four specific regulatory gene expression processes.
Main Results:
- RBPs and non-coding RNAs are critical for coordinating gene expression.
- Certain RNA regulators, like splice factors, are identified as cancer vulnerabilities.
- Functional genomics screens are effective for identifying functional phenotypes and genetic dependencies in cancer cells.
Conclusions:
- A comprehensive understanding of RNA regulatory mechanisms is essential for cancer research.
- Investigating the RNA lifecycle offers insights into tumor biology and potential therapeutic targets.
- Functional genomics accelerates the discovery of RNA-mediated gene expression control in cancer.
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