Highlights

Go or no-go?

1 Feb 2011

The crystal structure of the Dom34–Hbs1 complex reveals how cells recognize and remove defective messenger RNA with stalled elongation through ‘no-go’ decay

Crystal structure of the Dom34–Hbs1 complex

Crystal structure of the Dom34–Hbs1 complex

From Ref. 1. © 2010 R. Parker, H. Song

Protein synthesis is an extremely complex process. Ribosomes, which read the genetic codes of messenger RNA (mRNA) and use the information to make proteins, often encounter defective mRNA that hamper the translation process. Because of this, cells have evolved several mechanisms to detect and degrade defective mRNA. A recently identified mechanism, known as ‘no-go’ decay (NGD), targets mRNA with stem-loops—side branches that interrupt the translation elongation process—and is essential for maintaining the fidelity and quality of translation.

Studies on budding yeasts and fruit flies have identified Dom34 and Hbs1—the paralogs of peptide release factors eRF1 and eRF3—as two proteins required for eliminating mRNA with stem-loops through NGD. Structural analysis of yeast Dom34 has shown that the protein is similar to eRF1 in domains M and C but not in N. The relative orientation of the domains suggests that Dom34 might bind Hbs1 to form a complex (pictured) that promotes translation termination and commits the mRNA to NGD, in the same way as the eRF1–eRF3 complex promotes normal translation termination. This hypothesis, however, has never been confirmed.

Haiwei Song and co-workers at the A*STAR Institute of Molecular and Cell Biology have now shed light on the role of Dom34–Hbs1 in NGD by obtaining the crystal structure of Dom34–Hbs1 from fission yeast. They found that overall, the structure is similar to that of eRF1–eRF3, and that Dom34 and Hbs1 show similar biochemical properties to those of eRF1 and eRF3. The results suggest that Dom34–Hbs1 binds to the ribosomal A site where the complex plays a role in preventing translation elongation and promoting mRNA cleavage as an alternative event to NGD.

If Dom34–Hbs1 provides an alternative fate to NGD for ribosomes with stalled translation, it should be possible for the ribosome to undertake mRNA cleavage and NGD at strong translational pauses without Dom34–Hbs1. Consistent with this model, the researchers observed that NGD can be triggered by mRNA with a long error code that strongly blocks translation elongation, in the absence of the Dom34–Hbs1 complex.

Song and his co-workers are now looking at how Dom34–Hbs1 functions in the context of stalled ribosomes. “Specifically, we would like to know how Dom34–Hbs1 binds to the stalled ribosome and triggers NGD, using techniques such as X-ray crystallography and electron microscopy,” says Song. “We hope that these studies will reveal the molecular mechanism of NGD.”

The A*STAR-affiliated researchers contributing to this research are from the Institute of Molecular and Cell Biology.

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References

Chen, L. et al. Structure of the Dom34–Hbs1 complex and implications for no-go decay. Nature Structural and Molecular Biology 17, 1233–1241 (2010). | article

This article was made for A*STAR Research by Nature Research Custom Media, part of Springer Nature