Recruitment of the m⁶A/m6Am demethylase FTO to target RNAs by the telomeric zinc finger protein ZBTB48.

ABSTRACT:

Background

N6-methyladenosine (m6A), the most abundant internal modification on eukaryotic mRNA, and N6, 2'-O-dimethyladenosine (m6Am), are epitranscriptomic marks that function in multiple aspects of posttranscriptional regulation. Fat mass and obesity-associated protein (FTO) can remove both m⁶A and m6Am; however, little is known about how FTO achieves its substrate selectivity.

Results

Here, we demonstrate that ZBTB48, a C2H2-zinc finger protein that functions in telomere maintenance, associates with FTO and binds both mRNA and the telomere-associated regulatory RNA TERRA to regulate the functional interactions of FTO with target transcripts. Specifically, depletion of ZBTB48 affects targeting of FTO to sites of m6A/m6Am modification, changes cellular m6A/m6Am

SUBMITTER: Nabeel-Shah S 

PROVIDER: S-EPMC11414060 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature