Gain of additional BIRC3 protein functions through 3ʹ-UTR-mediated protein complex formation Journal Article


Authors: Lee, S. H.; Mayr, C.
Article Title: Gain of additional BIRC3 protein functions through 3ʹ-UTR-mediated protein complex formation
Abstract: Alternative 3ʹ untranslated regions (3ʹ UTRs) are widespread, but their functional roles are largely unknown. We investigated the function of the long BIRC3 3ʹ UTR, which is upregulated in leukemia. The 3ʹ UTR does not regulate BIRC3 protein localization or abundance but is required for CXCR4-mediated B cell migration. We established an experimental pipeline to study the mechanism of regulation and used mass spectrometry to identify BIRC3 protein interactors. In addition to 3ʹ-UTR-independent interactors involved in known BIRC3 functions, we detected interactors that bind only to BIRC3 protein encoded from the mRNA with the long 3ʹ UTR. They regulate several functions, including CXCR4 trafficking. We further identified RNA-binding proteins differentially bound to the alternative 3ʹ UTRs and found that cooperative binding of Staufen and HuR mediates 3ʹ-UTR-dependent complex formation. We show that the long 3ʹ UTR is required for the formation of specific protein complexes that enable additional functions of BIRC3 protein beyond its 3ʹ-UTR-independent functions. Lee and Mayr show that the E3 ligase BIRC3 has several different functions that are exclusively accomplished by BIRC3 protein encoded from the mRNA transcript containing the long, but not the short, 3ʹ UTR. 3ʹ-UTR-dependent protein functions are caused by BIRC3 protein complexes that require the long 3ʹ UTR for their formation. © 2019 Elsevier Inc.
Keywords: rna-binding proteins; cll; 3′-utr-dependent protein functions; 3′-utr-facilitated protein complex assembly; 3′-utr-independent protein functions; alternative 3′ utrs; b cell migration; cxcr4 receptor trafficking; e3 ubiquitin ligase birc3; protein multi-functionality
Journal Title: Molecular Cell
Volume: 74
Issue: 4
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2019-05-16
Start Page: 701
End Page: 712.e9
Language: English
DOI: 10.1016/j.molcel.2019.03.006
PUBMED: 30948266
PROVIDER: scopus
PMCID: PMC6581197
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Christine Mayr
    16 Mayr
  2. Shih-Han Lee
    7 Lee