RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence

Science. 2016 Apr 22;352(6284):453-9. doi: 10.1126/science.aad5978.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Butyrate Response Factor 1
  • Cyclins
  • Immunoglobulin mu-Chains
  • Nuclear Proteins
  • Pre-B Cell Receptors
  • RNA, Messenger
  • RNA-Binding Proteins
  • Tristetraprolin
  • Zfp36 protein, mouse
  • Zfp36l1 protein, mouse