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N 6 ‐methyladenosine modification of lncRNA Pvt1 governs epidermal stemness
Author(s) -
Lee Jimmy,
Wu Yuchen,
Harada Bryan T,
Li Yuanyuan,
Zhao Jing,
He Chuan,
Ma Yanlei,
Wu Xiaoyang
Publication year - 2021
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020106276
Subject(s) - library science , gerontology , medicine , computer science
Dynamic chemical modifications of RNA represent novel and fundamental mechanisms that regulate stemness and tissue homeostasis. Rejuvenation and wound repair of mammalian skin are sustained by epidermal progenitor cells, which are localized within the basal layer of the skin epidermis. N 6 ‐methyladenosine (m 6 A) is one of the most abundant modifications found in eukaryotic mRNA and lncRNA (long noncoding RNA). In this report, we survey changes of m 6 A RNA methylomes upon epidermal differentiation and identify Pvt1 , a lncRNA whose m 6 A modification is critically involved in sustaining stemness of epidermal progenitor cells. With genome‐editing and a mouse genetics approach, we show that ablation of m 6 A methyltransferase or Pvt1 impairs the self‐renewal and wound healing capability of skin. Mechanistically, methylation of Pvt1 transcripts enhances its interaction with MYC and stabilizes the MYC protein in epidermal progenitor cells. Our study presents a global view of epitranscriptomic dynamics that occur during epidermal differentiation and identifies the m 6 A modification of Pvt1 as a key signaling event involved in skin tissue homeostasis and wound repair.