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RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence. 2016
Alison Galloway, and
Alexander Saveliev, and
Sebastian Łukasiak, and
Daniel J Hodson, and
Daniel Bolland, and
Kathryn Balmanno, and
Helena Ahlfors, and
Elisa Monzón-Casanova, and
Sara Ciullini Mannurita, and
Lewis S Bell, and
Simon Andrews, and
Manuel D Díaz-Muñoz, and
Simon J Cook, and
Anne Corcoran, and
Martin Turner
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK.
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.
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