Mapping the path of destruction

Genome-wide analysis reveals details of RNA degradation proteins interacting with their targets.
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Cartoon of RNA. Image credit: Bruce Blaus (CC BY 3.0)

Cells contain a large group of DNA-like molecules called RNAs. While DNA stores and preserves information, RNA influences how cells use and regulate that information. As such, regulating the quantities of different RNAs is a key part of how cells survive, grow, adapt and respond to changes. For example, messenger RNAs (or mRNAs for short) carry genetic information from DNA which the cell reads to produce proteins. RNAs that are not needed can be degraded and removed from the cell by RNA degradation proteins.

Most RNA degradation proteins need to be able to bind to RNA in order to work. A technique called “photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation”, often shortened to PAR-CLIP, can detect these proteins on their targets. The PAR-CLIP technique irreversibly links RNA-binding proteins to RNA and then collects those proteins and their bound RNAs for analysis. As with DNA, the RNAs can be identified using genetic sequencing. Degradation often starts at RNA ends, where specialized structures protect the RNA from accidental damage.

Using PAR-CLIP, Sohrabi-Jahromi, Hofmann et al performed a detailed study of 30 RNA degradation proteins in the yeast Saccharomyces cerevisiae. The results highlight the specialization of different proteins to different groups of RNAs. One group of proteins, for example, remove the protective ‘cap’ structure at the start of RNAs. Those mRNAs that are not efficiently producing proteins attracted a lot of these cap-removing proteins. The findings also identify proteins involved in RNA degradation in the cell nucleus – the compartment that houses most of the cell’s DNA.

Together these findings provide an extensive data resource for cell biologists. It offers many links between different RNAs and their degradation proteins. Understanding these key cellular processes helps to reveal more about the mechanisms underlying all of biology. It can also shed light on what happens when these processes fail and the diseases that may result.