Abstract
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.
MeSH terms
-
Animals
-
B-Lymphocytes / immunology*
-
Butyrate Response Factor 1
-
Cell Adhesion / genetics*
-
Cell Adhesion / immunology
-
Cell Movement / genetics*
-
Cell Movement / immunology
-
Enzyme-Linked Immunosorbent Assay
-
Flow Cytometry
-
Fluorescent Antibody Technique
-
Gene Expression Regulation / genetics
-
High-Throughput Nucleotide Sequencing
-
Interferon Regulatory Factors / genetics
-
Kruppel-Like Transcription Factors / genetics
-
Lymphoid Tissue / cytology
-
Lymphoid Tissue / immunology
-
Mice
-
Nuclear Proteins / genetics*
-
Nuclear Proteins / immunology
-
Phenotype
-
RNA-Binding Proteins / genetics*
-
RNA-Binding Proteins / immunology
-
Real-Time Polymerase Chain Reaction
-
Sequence Analysis, RNA
-
Signal Transduction
Substances
-
Butyrate Response Factor 1
-
Interferon Regulatory Factors
-
Klf2 protein, mouse
-
Kruppel-Like Transcription Factors
-
Nuclear Proteins
-
RNA-Binding Proteins
-
Zfp36l1 protein, mouse
-
interferon regulatory factor-8