Mapping the RNA interactome of DDX5 and its rewiring by the K144N mutation in the RNA helicase domain
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ABSTRACT:
PROVIDER: PRJNA1297760 | ENA |
REPOSITORIES: ENA
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Project description:DDX5 is a multifunctional RNA helicase that regulates RNA metabolism and gene expression programs relevant to cancer and antiviral responses. Despite its importance, the RNA-binding landscape of DDX5 remains poorly defined. Here, we use CLIP-seq to systematically map the endogenous RNA interactome of DDX5 and to determine how it is altered by the K144N point mutation within the conserved RNA helicase domain.
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Project description:DDX5 is a founding member of the DEAD-box RNA helicase family, which are a group of enzymes that regulate ribonucleoprotein (RNP) formation and function in every aspect of RNA metabolism. Our lab previously found that DDX5 is involved in energy homeostasis, a process altered in many cancers. Small cell lung cancer (SCLC) is an understudied cancer type that lacks effective treatment. Therefore, we investigated the roles of DDX5 in SCLC. We show here that DDX5 is overexpressed in SCLC cell lines. Depletion of DDX5 results in reduced growth and mitochondrial dysfunction in the chemoresistant SCLC cell line H69AR. The latter is evidenced by downregulation of genes involved in oxidative phosphorylation and impaired oxygen consumption,. Interestingly, depletion of DDX5 specifically leads to reduction of intracellular succinate, a TCA intermediate that serves as a direct electron donor to mitochondrial complex II. Taken together, we propose that the oncogenic role of DDX5 is at least in part manifested through upregulation of respiration to support the energy demands of cancer cells. This also suggests that defects in RNP remodeling are connected to energy metabolism and carcinogenesis.
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Project description:Alternative splicing profiling of apopotosis related genes in human HeLa cells (cervical cancer cell line) transfected with a plasmid expressing shRNAs targetting p68 helicase (DDX5, DEAD (Asp-Glu-Ala-Asp) box polypeptide 5) cloned into the pSuper expression vector compared to empty vector. Keywords: treated vs. untreated comparison; alternative splicing
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