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USER TALK: How TDP-43 Condensation Modulates its RNA Processing and How This is Relevant for ALS

USER TALK: How TDP-43 Condensation Modulates its RNA Processing and How This is Relevant for ALS ABSTRACT: TDP-43 is a central RNA binding protein (RBP) involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Post-mortem tissue from about 97 percent of individuals with ALS presents TDP-43 aggregates, and TDP-43 proteinopathy is also common in other neurodegenerative diseases such as Dementia. Mutations in TDP-43 that cause ALS affect its condensation properties. Less is known about the role of TDP-43 condensation in the selection of specific endogenous RNA binding sites, and thereby regulation of RNAs. To address the question of TDP-43’s RNA specificity, Martina Hallegger and colleagues created different TDP-43 variants in several cell systems. They introduced deletions and mutations into the C-terminal intrinsically disordered region (IDR) of TDP-43 that change the condensation properties on a gradient from negative to positive effects both in vitro and in vivo. Using UV crosslinking and immunoprecipitation (iCLIP) and 3′ mRNA-seq, the team showed that TDP-43 condensation promotes its efficient assembly on a subset of RNA binding sites that are characterized by unique sequence features, including a highly multivalent arrangement of GU-rich motifs. SPEAKER: Martina Hallegger, PhD RNA-network Biochemist The Francis Crick Institute FOR MORE INFORMATION: Learn more about QuantSeq 3‘ mRNA-Seq Library Prep Kit: https://www.lexogen.com/quantseq-3mrn... Learn more about Lexogen products: https://www.lexogen.com/products/ FOLLOW US: Facebook - / lexogen Twitter - / lexogen LinkedIn - / lexogen-gmbh Instagram - / lexogen

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