The MiR-15 Family Reinforces the Transition from Proliferation to Differentiation in Pre-B Cells

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2017 Jul 15

PMID 28705801

Citations 21

Authors

Silke E Lindner

Michael Lohmuller

Bianka Kotkamp

Fabian Schuler

Zeynep Knust

Andreas Villunger

Sebastian Herzog

Affiliations

Soon will be listed here.

Abstract

Precursor B lymphocytes expand upon expression of a pre-B cell receptor (pre-BCR), but then transit into a resting state in which immunoglobulin light chain gene recombination is initiated. This bi-phasic sequence is orchestrated by the IL-7 receptor (IL-7R) and pre-BCR signaling, respectively, but little is known about microRNAs fine-tuning these events. Here, we show that pre-B cells lacking miR-15 family functions exhibit prolonged proliferation due to aberrant expression of the target genes cyclin E1 and D3. As a consequence, they fail to trigger the transcriptional reprogramming normally accompanying their differentiation, resulting in a developmental block at the pre-B cell stage. Intriguingly, our data indicate that the miR-15 family is suppressed by both IL-7R and pre-BCR signaling, suggesting it is actively integrated into the regulatory circuits of developing B cells. These findings identify the miR-15 family as a novel element required to promote the switch from pre-B cell proliferation to differentiation.

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