PRL3-DDX21 Transcriptional Control of Endolysosomal Genes Restricts Melanocyte Stem Cell Differentiation #MMPMID32652076
Johansson JA; Marie KL; Lu Y; Brombin A; Santoriello C; Zeng Z; Zich J; Gautier P; von Kriegsheim A; Brunsdon H; Wheeler AP; Dreger M; Houston DR; Dooley CM; Sims AH; Busch-Nentwich EM; Zon LI; Illingworth RS; Patton EE
Dev Cell 2020[Aug]; 54 (3): 317-332.e9 PMID32652076show ga
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.
free
free
free
Dev+Cell 2020 ; 54 (3): 317-332.e9
