Recruitment of the m6A/m6Am demethylase FTO to target RNAs by the telomeric zinc finger protein ZBTB48.
Genome Biol
; 25(1): 246, 2024 Sep 19.
Article
in En
| MEDLINE
| ID: mdl-39300486
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 levels and, consequently, alters decay rates of target RNAs. ZBTB48 ablation also accelerates growth of HCT-116 colorectal cancer cells and modulates FTO-dependent regulation of Metastasis-associated protein 1 (MTA1) transcripts by controlling the binding to MTA1 mRNA of the m6A reader IGF2BP2.CONCLUSIONS:
Our findings thus uncover a previously unknown mechanism of posttranscriptional regulation in which ZBTB48 co-ordinates RNA-binding of the m6A/m6Am demethylase FTO to control expression of its target RNAs.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adenosine
/
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
Limits:
Humans
Language:
En
Journal:
Genome Biol
/
Genome biol
/
Genome biology (Online)
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA
Year:
2024
Document type:
Article
Affiliation country:
Canada
Country of publication:
United kingdom