Hitomi Takada, Takahiro Kawana, Yuzuru Ito, Reiko F. Kikuno, Hiroshi Mamada, Toshiyuki Araki, Hisashi Koga, Makoto Asashima, and Masanori Taira
Post-transcriptional control by RNA-binding proteins is a precise way to
assure appropriate levels of gene expression. Here, we identify a novel mRNA
regulatory system involving Mex3b (RKHD3) and demonstrate its role in FGF
signaling. mex3b mRNA has a 3' long conserved UTR, named
3'LCU, which contains multiple elements for both mRNA destabilization
and translational enhancement. Notably, Mex3b promotes destabilization of its
own mRNA by binding to the 3'LCU, thereby forming a negative
autoregulatory loop. The combination of positive regulation and negative
autoregulation constitutes a fine-tuning system for post-transcriptional
control. In early embryogenesis, Mex3b is involved in anteroposterior
patterning of the neural plate. Consistent with this, Mex3b can attenuate FGF
signaling and destabilize mRNAs for the FGF signaling components Syndecan 2
and Ets1b through their 3' UTRs. These data suggest that the
3'LCU-mediated fine-tuning system determines the appropriate level of
mex3b expression, which in turn contributes to neural patterning
through regulating FGF signaling. |