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RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence.

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Galloway, Alison 
Saveliev, Alexander 
Łukasiak, Sebastian 
Hodson, Daniel J 
Bolland, Daniel 


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.



Animals, B-Lymphocytes, Butyrate Response Factor 1, Conserved Sequence, Cyclins, G1 Phase, Gene Expression Regulation, Immunoglobulin mu-Chains, Mice, Mice, Inbred C57BL, Mice, Knockout, Nuclear Proteins, Pre-B Cell Receptors, RNA, Messenger, RNA-Binding Proteins, Resting Phase, Cell Cycle, S Phase, Selection, Genetic, Transcription, Genetic, Tristetraprolin, V(D)J Recombination

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American Association for the Advancement of Science (AAAS)
Medical Research Council (MR/M008584/1)
Medical Research Council (MC_PC_12009)
This work was funded by the Biotechnology and Biological Sciences Research Council, a Medical Research Council CASE studentship with GSK, an MRC centenary award (A.G) and project grants from Bloodwise. DJH was supported by a Medical Research Council Clinician Scientist Fellowship