604 RNA methylation facilitates the repair of UV-induced DNA damage and suppresses photocarcinogenesis
نویسندگان
چکیده
UV-induced DNA damage is repaired by nucleotide excision repair (NER) that corrects bulky helix-distorting lesions across the whole genome and essential for preventing mutagenesis skin cancer. Here we show METTL14 (methyltransferase-like 14), a critical component of m6A RNA methyltransferase complex, promotes through regulating mRNA methylation-mediated translation NER factor DDB2 suppresses tumorigenesis. Ultraviolet irradiation down-regulates protein NBR1-dependent selective autophagy. knockdown decreases abundance. Conversely, overexpression wild-type METTL14, but not its enzymatically inactive mutant, increases methylation transcripts. Adding reverses defect in cells, indicating facilitates translation. Similarly, YTHDF1, an reader promoting modified transcripts, decreased levels. Both YTHDF1 bind to transcript. In mice, skin-specific heterozygous deletion Furthermore, as well down-regulated human mouse tumors chronic UV skin, level associated with level, suggesting tumor-suppressive role UV-associated tumorigenesis association regulation. Taken together, these findings demonstrate target autophagy acts epitranscriptomic mechanism regulate photocarcinogenesis.
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2022
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2022.05.614