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RNA-binding proteins of the ZFP36 family are best known for inhibiting the expression of cytokines through binding to AU-rich elements in the 3' untranslated region and promoting mRNA decay. Here we identified an indispensable role for ZFP36L1 as the regulator of a post-transcriptional hub that determined the identity of marginal-zone B cells by promoting their proper localization and survival. ZFP36L1 controlled a gene-expression program related to signaling, cell adhesion and locomotion; it achieved this in part by limiting expression of the transcription factors KLF2 and IRF8, which are known to enforce the follicular B cell phenotype. These mechanisms emphasize the importance of integrating transcriptional and post-transcriptional processes by RNA-binding proteins for maintaining cellular identity among closely related cell types.

Original publication

DOI

10.1038/ni.3724

Type

Journal article

Journal

Nat Immunol

Publication Date

06/2017

Volume

18

Pages

683 - 693

Keywords

Animals, B-Lymphocytes, Cell Adhesion, Cell Movement, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Fluorescent Antibody Technique, Gene Expression Regulation, High-Throughput Nucleotide Sequencing, Interferon Regulatory Factors, Kruppel-Like Transcription Factors, Lymphoid Tissue, Mice, Nuclear Proteins, Phenotype, RNA-Binding Proteins, Real-Time Polymerase Chain Reaction, Sequence Analysis, RNA, Signal Transduction