Fujiwara, T. | bioRxiv Science

bioRxiv2019

Single-molecule analysis reveals the rapid effect of estradiol on the surface movement of AMPAR in live neurons

The gonadal steroid 17{beta}-estradiol (E2) rapidly alters glutamatergic neurotransmission, but its direct effect on the AMPA receptor (AMPAR) remains unknown. Live-cell single-molecule imaging experiments revealed that E2 rapidly and dose-dependently alters the surface movement of AMPAR via membrane estrogen receptors with distinct effects on somas and neurites. The effect of E2 on the surface mobility of AMPAR depends on the integrity of the cortical actin network.

neuroscience↗

bioRxiv2019

Codon Optimality Confers GC-Rich-Induced Stability to mRNAs in Humans

Codon bias has been implicated as one of the major factors contributing to mRNA stability in yeast. However, the effects of codon-bias on mRNA stability remain unclear in humans. Here we show that human cells possess a mechanism to modulate RNA stability through a unique codon bias different from that of yeast. Bioinformatics analysis showed that codons could be clustered into two distinct groups - codons with G or C at the third base position (GC3) and codons with either A or T at the third base position (AT3); the former stabilizing while the latter destabilizing mRNA. Quantification of codon bias showed that increased GC3 content entails proportionately higher GC content. Through bioinformatics, ribosome profiling and in vitro analysis, we show that decoupling of the effects of codon bias reveals two modes of mRNA regulation, GC3- and GC-content dependent. Employing an immunoprecipitation-based strategy, we identified ILF2 as an RNA binding protein that differentially regulates global mRNA abundances based on codon bias. Our results demonstrate that codon bias is a two-pronged system that governs mRNA abundance.

molecular biology↗