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RNA Binding Protein CELF2 Regulates Signal-Induced Alternative Polyadenylation by Competing with Enhancers of the Polyadenylation Machinery

Authors: 
Chatrikhi R, Mallory MJ, Gazzara MR, Agosto LM, Zhu WS, Litterman AJ, Ansel KM, Lynch KW
Citation: 
Cell Rep. 2019;28(11):P2795-806. doi:10.1016/j.celrep.2019.08.022
Abstract: 
The 3′ UTR (UTR) of human mRNAs plays a critical role in controlling protein expression and function. Importantly, 3′ UTRs of human messages are not invariant for each gene but rather are shaped by alternative polyadenylation (APA) in a cell state-dependent manner, including in response to T cell activation. However, the proteins and mechanisms driving APA regulation remain poorly understood. Here we show that the RNA-binding protein CELF2 controls APA of its own message in a signal-dependent manner by competing with core enhancers of the polyadenylation machinery for binding to RNA. We further show that CELF2 binding overlaps with APA enhancers transcriptome-wide, and almost half of 3′ UTRs that undergo T cell signaling-induced APA are regulated in a CELF2-dependent manner. These studies thus reveal CELF2 to be a critical regulator of 3′ UTR identity in T cells and demonstrate an additional mechanism for CELF2 in regulating polyadenylation site choice.
Organism or Cell Type: 
cell culture: Jurkat
Delivery Method: 
elecroporation