| First Author | Orellana EA | Year | 2021 |
| Journal | Mol Cell | Volume | 81 |
| Issue | 16 | Pages | 3323-3338.e14 |
| PubMed ID | 34352207 | Mgi Jnum | J:355249 |
| Mgi Id | MGI:6751479 | Doi | 10.1016/j.molcel.2021.06.031 |
| Citation | Orellana EA, et al. (2021) METTL1-mediated m(7)G modification of Arg-TCT tRNA drives oncogenic transformation. Mol Cell 81(16):3323-3338.e14 |
| abstractText | The emerging "epitranscriptomics" field is providing insights into the biological and pathological roles of different RNA modifications. The RNA methyltransferase METTL1 catalyzes N7-methylguanosine (m(7)G) modification of tRNAs. Here we find METTL1 is frequently amplified and overexpressed in cancers and is associated with poor patient survival. METTL1 depletion causes decreased abundance of m(7)G-modified tRNAs and altered cell cycle and inhibits oncogenicity. Conversely, METTL1 overexpression induces oncogenic cell transformation and cancer. Mechanistically, we find increased abundance of m(7)G-modified tRNAs, in particular Arg-TCT-4-1, and increased translation of mRNAs, including cell cycle regulators that are enriched in the corresponding AGA codon. Accordingly, Arg-TCT expression is elevated in many tumor types and is associated with patient survival, and strikingly, overexpression of this individual tRNA induces oncogenic transformation. Thus, METTL1-mediated tRNA modification drives oncogenic transformation through a remodeling of the mRNA "translatome" to increase expression of growth-promoting proteins and represents a promising anti-cancer target. |
