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RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence

by Díaz-Muñoz, Manuel D. , Hodson, Daniel J. , Andrews, Simon , Balmanno, Kathryn , Mannurita, Sara Ciullini , Bolland, Daniel , Monzón-Casanova, Elisa , Cook, Simon J. , Turner, Martin , Corcoran, Anne , Ahlfors, Helena , Galloway, Alison , Łukasiak, Sebastian , Saveliev, Alexander , Bell, Lewis S.

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

2016

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RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence

2016

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RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence

2016

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Journal Article

RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence

Díaz-Muñoz, Manuel D.,

Hodson, Daniel J.,

Andrews, Simon,

Balmanno, Kathryn,

Mannurita, Sara Ciullini,

Bolland, Daniel,

Monzón-Casanova, Elisa,

Cook, Simon J.,

Turner, Martin,

Corcoran, Anne,

Ahlfors, Helena,

Galloway, Alison,

Łukasiak, Sebastian,

Saveliev, Alexander,

Bell, Lewis S.

2016

Overview

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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Publisher

American Association for the Advancement of Science,The American Association for the Advancement of Science

Subject

Animals

/ Antigens

/ B-Lymphocytes - cytology

/ Butyrate Response Factor 1

/ Conserved Sequence

/ Cyclins - metabolism

/ G1 Phase - genetics