PUBLICATION

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

Authors
Johansson, J.A., Marie, K.L., Lu, Y., Brombin, A., Santoriello, C., Zeng, Z., Zich, J., Gautier, P., von Kriegsheim, A., Brunsdon, H., Wheeler, A.P., Dreger, M., Houston, D.R., Dooley, C.M., Sims, A.H., Busch-Nentwich, E.M., Zon, L.I., Illingworth, R.S., Patton, E.E.
ID
ZDB-PUB-200712-8
Date
2020
Source
Developmental Cell   54(3): 317-332.e9 (Journal)
Registered Authors
Brombin, Alessandro, Busch-Nentwich, Elisabeth, Dooley, Christopher, Patton, E. Elizabeth, Santoriello, Cristina, Zeng, Zhiqiang, Zon, Leonard I.
Keywords
DDX21, MITF, PRL3, PTP4A3, melanocyte stem cell, melanoma, regeneration, small-molecule screen, transcription elongation, zebrafish
MeSH Terms
  • Humans
  • Stem Cells/metabolism
  • Animals
  • Neoplasm Proteins/genetics
  • Neoplasm Proteins/metabolism*
  • Melanocytes/cytology*
  • Microphthalmia-Associated Transcription Factor/genetics
  • Cell Differentiation/genetics*
  • Zebrafish/metabolism
  • DEAD-box RNA Helicases/genetics
  • DEAD-box RNA Helicases/metabolism*
  • Protein Tyrosine Phosphatases/genetics
  • Protein Tyrosine Phosphatases/metabolism*
  • Melanoma/genetics
  • Melanoma/metabolism*
  • Mutation
  • Zebrafish Proteins/metabolism
  • Gene Expression Regulation, Developmental
(all 18)
PubMed
32652076 Full text @ Dev. Cell
Abstract
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.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Marker Marker Type Name
DsRedEFGDsRed
EGFPEFGEGFP
GFPEFGGFP
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Mapping
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Citation
Johansson, J.A., Marie, K.L., Lu, Y., Brombin, A., Santoriello, C., Zeng, Z., Zich, J., Gautier, P., von Kriegsheim, A., Brunsdon, H., Wheeler, A.P., Dreger, M., Houston, D.R., Dooley, C.M., Sims, A.H., Busch-Nentwich, E.M., Zon, L.I., Illingworth, R.S., Patton, E.E. (2020) PRL3-DDX21 Transcriptional Control of Endolysosomal Genes Restricts Melanocyte Stem Cell Differentiation. Developmental Cell. 54(3):317-332.e9.