The dorsal lingual epithelium,which is composed of taste buds and keratinocytes differentiated from K14^(+)basal cells,discriminates taste compounds and maintains the epithelial barrier.N6-methyladenosine(m^(6)A)is th...The dorsal lingual epithelium,which is composed of taste buds and keratinocytes differentiated from K14^(+)basal cells,discriminates taste compounds and maintains the epithelial barrier.N6-methyladenosine(m^(6)A)is the most abundant mRNA modification in eukaryotic cells.How METTL3-mediated m^(6)A modification regulates K14^(+)basal cell fate during dorsal lingual epithelium formation and regeneration remains unclear.Here we show knockout of Mettl3 in K14^(+)cells reduced the taste buds and enhanced keratinocytes.Deletion of Mettl3 led to increased basal cell proliferation and decreased cell division in taste buds.Conditional Mettl3 knock-in mice showed little impact on taste buds or keratinization,but displayed increased proliferation of cells around taste buds in a protective manner during post-irradiation recovery.Mechanically,we revealed that the most frequent m^(6)A modifications were enriched in Hippo and Wnt signaling,and specific peaks were observed near the stop codons of Lats1 and FZD7.Our study elucidates that METTL3 is essential for taste bud formation and could promote the quantity recovery of taste bud after radiation.展开更多
Methylation of adenosine base on the nitrogen-6 position (N6-methyladenosine, m^6A) is the most common and abundant modification on mRNA transcripts. This post-transcriptional modification was first described in the...Methylation of adenosine base on the nitrogen-6 position (N6-methyladenosine, m^6A) is the most common and abundant modification on mRNA transcripts. This post-transcriptional modification was first described in the 1970s in hepatoma cells (Desrosiers et al., 1974).展开更多
Recently an article published in Molecular Cell reveals the mechanism of a nuclear N6-methyladenosine(m^6A)reader,the YTH domain-containing protein 1(YTHDC1),in regulating pre-m RNA splicing[1].Meanwhile,two addit...Recently an article published in Molecular Cell reveals the mechanism of a nuclear N6-methyladenosine(m^6A)reader,the YTH domain-containing protein 1(YTHDC1),in regulating pre-m RNA splicing[1].Meanwhile,two additional articles published in Nature and Nature Chemical Biology report the展开更多
基金supported by the National Natural Science Foundation of China(81970913 and 82125006)。
文摘The dorsal lingual epithelium,which is composed of taste buds and keratinocytes differentiated from K14^(+)basal cells,discriminates taste compounds and maintains the epithelial barrier.N6-methyladenosine(m^(6)A)is the most abundant mRNA modification in eukaryotic cells.How METTL3-mediated m^(6)A modification regulates K14^(+)basal cell fate during dorsal lingual epithelium formation and regeneration remains unclear.Here we show knockout of Mettl3 in K14^(+)cells reduced the taste buds and enhanced keratinocytes.Deletion of Mettl3 led to increased basal cell proliferation and decreased cell division in taste buds.Conditional Mettl3 knock-in mice showed little impact on taste buds or keratinization,but displayed increased proliferation of cells around taste buds in a protective manner during post-irradiation recovery.Mechanically,we revealed that the most frequent m^(6)A modifications were enriched in Hippo and Wnt signaling,and specific peaks were observed near the stop codons of Lats1 and FZD7.Our study elucidates that METTL3 is essential for taste bud formation and could promote the quantity recovery of taste bud after radiation.
文摘Methylation of adenosine base on the nitrogen-6 position (N6-methyladenosine, m^6A) is the most common and abundant modification on mRNA transcripts. This post-transcriptional modification was first described in the 1970s in hepatoma cells (Desrosiers et al., 1974).
基金supported by the National Basic Research Program of China (973 ProgramGrant No.2014CB964900)the National Natural Science Foundation of China (Grant Nos.21432002,21372022,and 21210003)
文摘Recently an article published in Molecular Cell reveals the mechanism of a nuclear N6-methyladenosine(m^6A)reader,the YTH domain-containing protein 1(YTHDC1),in regulating pre-m RNA splicing[1].Meanwhile,two additional articles published in Nature and Nature Chemical Biology report the