Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs

Transfer RNA is heavily modified and plays a central role in protein synthesis and cellular functions. Here we demonstrate that ALKBH3 is a 1-methyladenosine (m(1)A) and 3-methylcytidine (m(3)C) demethylase of tRNA. ALKBH3 can promote cancer cell proliferation, migration and invasion. In vivo study...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Zhuojia, Qi, Meijie, Shen, Bin, Luo, Guanzheng, Wu, Yingmin, Li, Jiexin, Lu, Zhike, Zheng, Zhong, Dai, Qing, Wang, Hongsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
RNA and RNA-protein complexes
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411830/
https://www.ncbi.nlm.nih.gov/pubmed/30541109
http://dx.doi.org/10.1093/nar/gky1250
Descripción
Sumario:Transfer RNA is heavily modified and plays a central role in protein synthesis and cellular functions. Here we demonstrate that ALKBH3 is a 1-methyladenosine (m(1)A) and 3-methylcytidine (m(3)C) demethylase of tRNA. ALKBH3 can promote cancer cell proliferation, migration and invasion. In vivo study confirms the regulation effects of ALKBH3 on growth of tumor xenograft. The m(1)A demethylated tRNA is more sensitive to angiogenin (ANG) cleavage, followed by generating tRNA-derived small RNAs (tDRs) around the anticodon regions. tDRs are conserved among species, which strengthen the ribosome assembly and prevent apoptosis triggered by cytochrome c (Cyt c). Our discovery opens a potential and novel paradigm of tRNA demethylase, which regulates biological functions via generation of tDRs.

Ejemplares similares