Insights into the assembly and architecture of a Staufen-mediated mRNA decay (SMD)-competent mRNP.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31699982.
- Also identified by DOI 10.1038/s41467-019-13080-x and PMC identifier 6838198.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The mammalian Staufen proteins (Stau1 and Stau2) mediate degradation of mRNA containing complex secondary structures in their 3'-untranslated region (UTR) through a pathway known as Staufen-mediated mRNA decay (SMD). This pathway also involves the RNA helicase UPF1, which is best known for its role in the nonsense-mediated mRNA decay (NMD) pathway. Here we present a biochemical reconstitution of the recruitment and activation of UPF1 in context of the SMD pathway. We demonstrate the involvement of UPF2, a core NMD factor and a known activator of UPF1, in SMD. UPF2 acts as an adaptor between Stau1 and UPF1, stimulates the catalytic activity of UPF1 and plays a central role in the formation of an SMD-competent mRNP. Our study elucidates the molecular mechanisms of SMD and points towards extensive cross-talk between UPF1-mediated mRNA decay pathways in cells.
Medical subject headings
- Cytoskeletal Proteins
- RNA Helicases
- RNA Stability
- RNA, Messenger
- RNA-Binding Proteins
- Ribonucleoproteins
- Trans-Activators