CRISPR and RNA editing

I find it somewhat satisfying that the field of RNA editing (in the broad sense) which I and my students worked on for so long is contributing, at least linguistically, to one of the most exciting gene modification techniques developed in recent years - CRISPR. Initially Doudna showed that joining two RNAs, one encoding a DNA nuclease and the other a short RNA sequence complementary to the site to be edited produced an RNA that could recognize and modify specific sites in genomic DNA. The mechanism of site specificity was simple base pairing and they used the term "guide RNA or gRNA" to describe this construct. This was the mechanism my lab had discovered in 1990 by which the insertion/deletion of uridine residues at precise sites in the cryptogenes encoded in maxicircle mitochondrial DNA of trypanosomatid parasites was achieved. We coined the term, guide RNA to describe short RNAs encoded mainly by the thousands of catenated minicircles in the kinetoplast mitochondria DNA which could recognize specific sites to be edited and recruit multiple protein complexes that precisely cleaved the mRNA, inserted uridines and then joined the two DNA fragments. Several additional “editing” phenomena were soon discovered that changed C to U in mammalian ApoB mRNA and changed encoded adenosine resides in multiple mammalian mRNAs to inosine, which behaved like guanosine. Again the site specificities, at least in ADAR editing, were determined by the mRNAs encoding complementary sequences in cis which acted by foldback to identify specific sites by base pairing and then recruiting ADAR adenosine deaminase enzymes. In fact, in our RNA editing Gordon Conferences at that time, the term “RNA editing” was used for both the trypanosomatid insertion/deletion of U’s and the method by which precise A’s were changed to G’s (functionally) or C’s to U. And now ADAR and APOBEC editing has solved one of the major problems of the CRISPR system by allowing the efficient production of specific nucleotide changes in mRNAs without non-specific changes elsewhere in the genome.
Truly, the incredible insight of Jim Watson and Francis Crick in their DNA double helix model in 1953 which was based on the base pairing of nucleotides in the two strands led to their understated ending comment in their Nature paper that it has not escaped their attention that this would lead to an elegant mechanism for DNA replication.