Termination codon readthrough of NNAT mRNA regulates calcium-mediated neuronal differentiation.

ABSTRACT: Termination codon readthrough (TCR) is a process in which ribosomes continue to translate an mRNA beyond a stop codon generating a C-terminally extended protein isoform. Here, we demonstrate TCR in mammalian NNAT mRNA, which encodes NNAT, a proteolipid important for neuronal differentiation. This is a programmed event driven by cis-acting RNA sequences present immediately upstream and downstream of the canonical stop codon and is negatively regulated by NONO, an RNA-binding protein known to promote neuronal differentiation. Unlike the canonical isoform NNAT, we determined that the TCR product (NNATx) does not show detectable interaction with the sarco/endoplasmic reticulum Ca²⁺-ATPase isoform 2 Ca²⁺ pump, cannot increase cytoplasmic Ca²⁺ levels, and therefo

SUBMITTER: Pandit M 

PROVIDER: S-EPMC10506107 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature