A cleaved METTL3 potentiates the METTL3-WTAP interaction and breast cancer progression.

ABSTRACT: N⁶-methyladenosine (m⁶A) methylation of RNA by the methyltransferase complex (MTC), with core components including METTL3-METTL14 heterodimers and Wilms' tumor 1-associated protein (WTAP), contributes to breast tumorigenesis, but the underlying regulatory mechanisms remain elusive. Here, we identify a novel cleaved form METTL3a (residues 239-580 of METTL3). We find that METTL3a is required for the METTL3-WTAP interaction, RNA m⁶A deposition, as well as cancer cell proliferation. Mechanistically, we find that METTL3a is essential for the METTL3-METTL3 interaction, which is a prerequisite step for recruitment of WTAP in MTC. Analysis of m⁶A sequencing data shows that depletion of METTL3a globally disrupts m⁶A deposition, an

SUBMITTER: Yan C 

PROVIDER: S-EPMC10435237 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature