title: Maintenance of the marginal-zone B cell compartment specifically requires the RNA-binding protein ZFP36L1.
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.
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.|Immune Receptor Activation Laboratory, The Francis Crick Institute, London, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Newman
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
authors.forename: Helena
authors.initials: H
authors.lastname: Ahlfors
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Saveliev
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
authors.forename: Alison
authors.identifier: 0000-0001-8780-0382
authors.initials: A
authors.lastname: Galloway
authors.affiliation: Department of Haematology, University of Cambridge, The Clifford Allbutt Building, Cambridge Biomedical Campus, Cambridge, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hodson
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Williams
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham, UK.
authors.forename: Gurdyal S
authors.identifier: 0000-0002-5605-0395
authors.initials: GS
authors.lastname: Besra
authors.affiliation: MRC Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham, UK.
authors.forename: Charlotte N
authors.initials: CN
authors.lastname: Cook
authors.affiliation: MRC Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham, UK.
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
authors.forename: Sarah E
authors.identifier: 0000-0002-3249-707X
authors.initials: SE
authors.lastname: Bell
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
authors.forename: Martin
authors.identifier: 0000-0002-3801-9896
authors.initials: M
authors.lastname: Turner
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D051817:Butyrate Response Factor 1; D002448:Cell Adhesion / Q000235:genetics* / Q000276:immunology; D002465:Cell Movement / Q000235:genetics* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D050835:Interferon Regulatory Factors / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D000099185:Interferon Regulatory Factor-8
chemical_list: D051817:Butyrate Response Factor 1; D050835:Interferon Regulatory Factors; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D000099185:Interferon Regulatory Factor-8; C498314:Klf2 protein, mouse; C488431:Zfp36l1 protein, mouse