RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence.
Progression through the stages of lymphocyte development requires coordination of the cell cycle. Such coordination ensures genomic integrity while cells somatically rearrange their antigen receptor genes [in a process called variable-diversity-joining (VDJ) recombination] and, upon successful rearrangement, expands the pools of progenitor lymphocytes. Here we show that in developing B lymphocytes, the RNA-binding proteins (RBPs) ZFP36L1 and ZFP36L2 are critical for maintaining quiescence before precursor B cell receptor (pre-BCR) expression and for reestablishing quiescence after pre-BCR-induced expansion. These RBPs suppress an evolutionarily conserved posttranscriptional regulon consisting of messenger RNAs whose protein products cooperatively promote transition into the S phase of the cell cycle. This mechanism promotes VDJ recombination and effective selection of cells expressing immunoglobulin-μ at the pre-BCR checkpoint.
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
Alison
A
Galloway
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
Alexander
A
Saveliev
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
Sebastian
S
Łukasiak
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK. Department of Haematology, University of Cambridge, The Clifford Allbutt Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0AH, UK.
Daniel J
DJ
Hodson
Laboratory of Nuclear Dynamics, The Babraham Institute, Cambridge CB22 3AT, UK.
Daniel
D
Bolland
Laboratory of Signalling, The Babraham Institute, Cambridge CB22 3AT, UK.
Kathryn
K
Balmanno
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
Helena
H
Ahlfors
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK. Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
Elisa
E
Monzón-Casanova
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
Sara Ciullini
SC
Mannurita
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
Lewis S
LS
Bell
Bioinformatics Group, The Babraham Institute, Cambridge CB22 3AT, UK.
Simon
S
Andrews
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
Manuel D
MD
Díaz-Muñoz
Laboratory of Signalling, The Babraham Institute, Cambridge CB22 3AT, UK.
Simon J
SJ
Cook
Laboratory of Nuclear Dynamics, The Babraham Institute, Cambridge CB22 3AT, UK.
Anne
A
Corcoran
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
Martin
M
Turner
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D051817:Butyrate Response Factor 1; D017124:Conserved Sequence; D016213:Cyclins / Q000378:metabolism; D016193:G1 Phase / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D054420:Pre-B Cell Receptors; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000502:physiology; D016196:S Phase / Q000235:genetics / Q000502:physiology*; D012641:Selection, Genetic; D014158:Transcription, Genetic; D051816:Tristetraprolin / Q000235:genetics / Q000502:physiology*; D060152:V(D)J Recombination
D051817:Butyrate Response Factor 1; D016213:Cyclins; D007148:Immunoglobulin mu-Chains; D009687:Nuclear Proteins; D054420:Pre-B Cell Receptors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051816:Tristetraprolin; C497553:Zfp36 protein, mouse; C488431:Zfp36l1 protein, mouse