A team of scientists have discovered that the neuronal transport factor Staufen2 scans and binds to its target transcripts in a much more complex manner than previously thought. RNA is transported within highly complex protein-RNA particles whose structure and specificity are still poorly understood. The team's findings, recently published in the journal Nature Communications, opens up new approaches to improve our understanding of the process.
Staufen2 is a neuronal RNA-binding protein that plays an important role in the differentiation of neural progenitor cells during neurogenesis. In addition, it is a key factor in the transport of RNA to synapses and is therefore important for synaptic plasticity, the basis of memory and memory formation.
The team showed that RNA-binding domains (dsRBDs) 1 and 2 of the mStau2 protein bond to mRNA with the same affinity and kinetics as domains 3 and 4. It was previously thought that the latter were in themselves sufficient for mRNA binding. While RNA recognition by each of these so-called tandem domains is transient, all four RNA-binding domains recognize their target RNA with a high degree of stability.
Previous studies had suggested that only two RNA binding domains in Staufen2, namely dsRBD 3 and 4, are responsible for binding. Despite this, until now it proved impossible to reproduce stable binding required for RNA transport in the test tube. "That problem has been solved," says the author, "because it is now clear that dsRBDs 1 and 2 are also needed to create a stable complex.
Using various biochemical and biophysical techniques, we were able to explain the behavior of dsRBD 1 and 2 ". "It turns out that Staufen2 recognizes its target RNAs in a much more complex way than previously thought," adds the lead author of the article. "Staufen2 scans and binds to its transcripts with four RNA-binding domains in total ".
The Staufen2 protein plays a key role in memory formation and memory persistence, though the process is still not well understood. In an aging society, research on this topic is of paramount importance as it improves our understanding of the molecular underpinnings and principles of learning and memory.
https://www.helmholtz-muenchen.de/en/aktuelles/latest-news/press-information-news/article/46188/index.html
https://www.nature.com/articles/s41467-019-09655-3
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fstaufen2-mediated-rna&filter=22
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