Genome complexity: squid modify neuron DNA with RNA (Introduction)

by David Turell @, Wednesday, March 25, 2020, 19:50 (11 days ago) @ David Turell

Just as our cells self-modify DNA to perform specific functions, squid are found to modify DNA in their neurons:

Title of article: "Spatially regulated editing of genetic information within a neuron"

In eukaryotic cells, with the exception of the specialized genomes of mitochondria and plastids, all genetic information is sequestered within the nucleus. This arrangement imposes constraints on how the information can be tailored for different cellular regions, particularly in cells with complex morphologies like neurons. Although messenger RNAs (mRNAs), and the proteins that they encode, can be differentially sorted between cellular regions, the information itself does not change. RNA editing by adenosine deamination can alter the genome’s blueprint by recoding mRNAs; however, this process too is thought to be restricted to the nucleus. In this work, we show that ADAR2 (adenosine deaminase that acts on RNA), an RNA editing enzyme, is expressed outside of the nucleus in squid neurons. Furthermore, purified axoplasm exhibits adenosine-to-inosine activity and can specifically edit adenosines in a known substrate. Finally, a transcriptome-wide analysis of RNA editing reveals that tens of thousands of editing sites (>70% of all sites) are edited more extensively in the squid giant axon than in its cell bodies. These results indicate that within a neuron RNA editing can recode genetic information in a region-specific manner."

In the discussion:

"Data from this paper suggest that region-specific RNA editing occurs in squid axons. We base this claim on the following findings: (i) SqADAR2 protein is present in the cytoplasm of nerve cell bodies in both the SG of the PNS and the OL of the CNS; (ii) axoplasm from the GA can catalyze the hydrolytic deamination of A→I in a perfect RNA duplex; (iii) axoplasm from the GA can catalyze site-specific RNA editing in a squid K+ channel substrate; and (iv) RNA editing at known sites is generally higher in the GA than its cell bodies. Editing almost certainly occurs in the nucleus as well. SqADAR2 is clearly present in many nuclei across the regions of the nervous system that were surveyed in this study. Therefore, based on these data we cannot exclude the possibility that all editing occurs in the nucleus and that edited messages bound to SqADAR2B get preferentially sorted to the axon.


"In this study, we examined differential editing between two regions: the GFL somata and the initial segment of the GA. SqADAR2 was seen, however, in the synaptic zone of the OL’s plexiform layer as well. It should be noted that the RNA isolated from the GA could have been in transit to other regions. The extent to which it is edited once reaching its destination, or whether it gets edited further after arriving, is unknown. Thus, it is likely that region-specific editing is more complicated in cephalopods than our data have uncovered. Does extranuclear recoding occur in other organisms? ADAR localization has only been examined in a few cases, under a small number of experimental conditions. Even in mammals, ADAR1 p150 is expressed in the cytoplasm and editable substrates occur within mature mRNAs. How this process is regulated in cephalopods should shed light on how RNA editing can be used to tune cellular physiology"

Comment: The octopus is known to do the same thing:

"The octopus has a very large genome and can edit their own genomes, altering their RNA. They “ do not always follow their genetic instructions to the letter:'”

So we see Shapiro's bacterial work passed on in evolution, but not speciation so far. The authors are surprised how much is done outside the nucleus itself. Note the title reference to 'genetic information'.

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