RNA - changing squids



A species of squid has been observed editing its own RNA to an amazing extent, creating the capacity to respond to changes in its environment by altering its proteins and therefore its entire body. The discovery could explain why squid seem to be one of the few species doing well out of the damage humans are inflicting on the oceans and climate.

Messenger RNA (mRNA) transfers genetic information from our DNA to the ribosomes that synthesize proteins within cells. Most of the time, the mRNA is transcribed reliably, serving as an instructional memo for protein building. As a paper published in eLife puts it: “The central dogma of biology maintains that genetic information passes faithfully from DNA to RNA to proteins.”

Occasionally, however, the memo gets changed in transmission. The paper describes this as “organisms using RNA as a canvas to modify and enrich the flow of information.” Simply by changing adenosine to inosine, animals can alter the shape, and therefore the function, of their proteins. Mammals don't seem to do this much. Fruit flies are far more enthusiastic users of this tool, editing 3% of their mRNAs in this way.

Evidence has come to light suggesting octopus and squid may be even more frequent users of A-to-I RNA editing than fruit flies, responding to temperature changes by altering the way they express many of their proteins.

Until now, however, no one had conducted a systematic study of the extent to which cephalapods adapt in this way. In the eLife paper, Dr. Eli Eisenberg of Tel Aviv University specifically explores mRNA editing in Doryteuthis pealeii, the longfin inshore squid.

For species that have not had their genomes sequenced yet, Eisenberg created a new technique that detects sites where recoding occurs. He found 57,108 recoding sites in the squid's nervous system—these affected more than half the proteins studied, with the percentage even higher in genes that relate to the functioning of the brain.

"It was astonishing to find that 60% of the squid RNA transcripts were edited,” says Eisenberg. "Why do squid edit to such an extent? One theory is that they have an extremely complex nervous system, exhibiting behavioral sophistication unusual for invertebrates. They may also utilize this mechanism to respond to changing temperatures and other environmental parameters."

The implications go beyond just another example of why squid are awesome. “There may be implications for us as well. Human diseases are often the result of 'misfolded' proteins, which often become toxic,” says Eisenberg. “Therefore the question of treating the misfolded proteins, likely to be generated by such an extensive recoding as exhibited in the squid cells, is very important for future therapeutic approaches. Does the squid have some mechanism we can learn from?"

Consequently, Eisenberg says, "We would like to understand better how prevalent this phenomenon is in the animal world. How is it regulated? How is it exploited to confer adaptability?"

Credit: Alon et al. (A) Squid RNA-seq data is used to detect cases where the RNA is edited. (B) ‘Weak’ and ‘strong’ editing sites are detected by comparing RNA and DNA reads from the same animal to the ORFs from the transcriptome. ‘Weak’ editing sites were detected by observing the minority of the RNA reads to differ from the consensus transcriptome nucleotide. ‘Strong’ editing sites, where the consensus transcriptome includes the edited nucleotide, were detected by observing all DNA reads to differ from the transcriptome nucleotide.

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