RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence

A Galloway, A Saveliev, S Łukasiak, DJ Hodson… - Science, 2016 - science.org
A Galloway, A Saveliev, S Łukasiak, DJ Hodson, D Bolland, K Balmanno, H Ahlfors…
Science, 2016science.org
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) …
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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