IGF2BP3 promotes mRNA degradation through internal m<sup>7</sup>G modification.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39198433.
- Also identified by DOI 10.1038/s41467-024-51634-w and PMC identifier 11358264.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Recent studies have suggested that mRNA internal m<sup>7</sup>G and its writer protein METTL1 are closely related to cell metabolism and cancer regulation. Here, we identify that IGF2BP family proteins IGF2BP1-3 can preferentially bind internal mRNA m<sup>7</sup>G. Such interactions, especially IGF2BP3 with m<sup>7</sup>G, could promote the degradation of m<sup>7</sup>G target transcripts in cancer cells. IGF2BP3 is more responsive to changes of m<sup>7</sup>G modification, while IGF2BP1 prefers m<sup>6</sup>A to stabilize the bound transcripts. We also demonstrate that p53 transcript, TP53, is m<sup>7</sup>G-modified at its 3'UTR in cancer cells. In glioblastoma, the methylation level and the half lifetime of the modified transcript could be modulated by tuning IGF2BP3, or by site-specific targeting of m<sup>7</sup>G through a dCas13b-guided system, resulting in modulation of cancer progression and chemosensitivity.
Medical subject headings
- 3' Untranslated Regions
- Glioblastoma
- RNA Stability
- RNA, Messenger
- RNA-Binding Proteins