PRL3-DDX21 Transcriptional Control of Endolysosomal Genes Restricts Melanocyte Stem Cell Differentiation.

Dev Cell 2020 Aug 10;54(3):317-332.e9. Epub 2020 Jul 10.

MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK; Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. Electronic address:

Melanocytes, replenished throughout life by melanocyte stem cells (MSCs), play a critical role in pigmentation and melanoma. Here, we reveal a function for the metastasis-associated phosphatase of regenerating liver 3 (PRL3) in MSC regeneration. We show that PRL3 binds to the RNA helicase DDX21, thereby restricting productive transcription by RNAPII at master transcription factor (MITF)-regulated endolysosomal vesicle genes. In zebrafish, this mechanism controls premature melanoblast expansion and differentiation from MSCs. In melanoma patients, restricted transcription of this endolysosomal vesicle pathway is a hallmark of PRL3-high melanomas. Our work presents the conceptual advance that PRL3-mediated control of transcriptional elongation is a differentiation checkpoint mechanism for activated MSCs and has clinical relevance for the activity of PRL3 in regenerating tissue and cancer.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.devcel.2020.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435699PMC
August 2020
9.708 Impact Factor

Publication Analysis

Top Keywords

endolysosomal vesicle
8
melanocyte stem
8
mechanism controls
4
controls premature
4
zebrafish mechanism
4
genes zebrafish
4
vesicle genes
4
premature melanoblast
4
melanoblast expansion
4
melanoma patients
4
mscs melanoma
4
differentiation mscs
4
expansion differentiation
4
regeneration prl3
4
mitf-regulated endolysosomal
4
ddx21 restricting
4
restricting productive
4
helicase ddx21
4
rna helicase
4
binds rna
4

Similar Publications