Exosome complex orchestrates developmental signaling to balance proliferation and differentiation during erythropoiesis

• Main Authors: Skye C McIver, Koichi R Katsumura, Elsa Davids, Peng Liu, Yoon-A Kang, David Yang, Emery H Bresnick
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2016-08-01
• Series: eLife
• Subjects: erythroid; progenitor; signaling; transcription
• Online Access: https://elifesciences.org/articles/17877

Since the highly conserved exosome complex mediates the degradation and processing of multiple classes of RNAs, it almost certainly controls diverse biological processes. How this post-transcriptional RNA-regulatory machine impacts cell fate decisions and differentiation is poorly understood. Previously, we demonstrated that exosome complex subunits confer an erythroid maturation barricade, and the erythroid transcription factor GATA-1 dismantles the barricade by transcriptionally repressing the cognate genes. While dissecting requirements for the maturation barricade in Mus musculus, we discovered that the exosome complex is a vital determinant of a developmental signaling transition that dictates proliferation/amplification versus differentiation. Exosome complex integrity in erythroid precursor cells ensures Kit receptor tyrosine kinase expression and stem cell factor/Kit signaling, while preventing responsiveness to erythropoietin-instigated signals that promote differentiation. Functioning as a gatekeeper of this developmental signaling transition, the exosome complex controls the massive production of erythroid cells that ensures organismal survival in homeostatic and stress contexts.