Circular RNAs trigger nonsense-mediated mRNA decay.

Circular RNAs (circRNAs) are covalently closed single-stranded RNAs produced predominantly through a back-splicing process. They play regulatory roles in various biological and physiological processes; however, the molecular mechanisms by which circRNAs operate remain unclear. Herein, we demonstrate that circRNAs facilitate rapid mRNA degradation through RNA-RNA interactions between circRNAs and the 3' untranslated regions (3' UTRs) of mRNAs.

Transcriptome-wide analysis for glucocorticoid receptor-mediated mRNA decay reveals various classes of target transcripts.

The glucocorticoid receptor (GR) can bind to DNA or RNA, eliciting transcriptional activation/repression or rapid messenger RNA (mRNA) degradation, respectively. Although GR-mediated transcriptional regulation has been well-characterized, the molecular details of rapid mRNA degradation induced by glucocorticoids are not yet fully understood. Here, we demonstrate that glucocorticoid-induced GR-mediated mRNA decay (GMD) takes place in the nucleus and the cytoplasm, acting on pre-mRNAs and mRNAs.

An interaction between eIF4A3 and eIF3g drives the internal initiation of translation.

An RNA structure or modified RNA sequences can provide a platform for ribosome loading and internal translation initiation. The functional significance of internal translation has recently been highlighted by the discovery that a subset of circular RNAs (circRNAs) is internally translated. However, the molecular mechanisms underlying the internal initiation of translation in circRNAs remain unclear.

UPF1 promotes rapid degradation of mA-containing RNAs.

N-methyladenosine (mA) is the most prevalent internal modification in eukaryotic mRNAs and affects RNA processing and metabolism. When YTHDF2, an mA-recognizing protein, binds to mA, it facilitates the destabilization of mA-containing RNAs (mA RNAs). Here, we demonstrate that upstream frameshift 1 (UPF1), a key factor for nonsense-mediated mRNA decay, interacts with YTHDF2, thereby triggering rapid degradation of mA RNAs.

Endoribonucleolytic Cleavage of mA-Containing RNAs by RNase P/MRP Complex.

N-methyladenosine (mA) is the most abundant internal modification in RNAs and plays regulatory roles in a variety of biological and physiological processes. Despite its important roles, the molecular mechanism underlying mA-mediated gene regulation is poorly understood. Here, we show that mA-containing RNAs are subject to endoribonucleolytic cleavage via YTHDF2 (mA reader protein), HRSP12 (adaptor protein), and RNase P/MRP (endoribonucleases).