Alu Behind Learning and Memory?

I’ve been wanting to comment on this article by Mattick and Mehler, but have just been too busy. Luckily, I just ran across a web article that borrows heavily from M&M’s article. I would encourage you to read the whole thing (if you can’t get your hands on M&M’s article, that is). Here are some excerpts:

Two classes of coincidental events stand out in the evolution of primates, the end result of which is to greatly expand the diversity of transcripts and proteins and to build the complex regulatory architecture required for human intellectual capacity. The first is the dramatic increase in RNA editing, a process that systematically alters the genetic messages transcribed from the genome, creating new coding and non-coding RNAs, and hence new proteins as well as RNAi (interfering RNA) species that regulate networks of genes. The second is the expansion of primate-specific Alu retrotransposons, which multiply through RNA intermediates that are reverse-transcribed and inserted into the genome. It so happens that the increase in RNA editing in primates occurs almost entirely within primate-specific Alu elements.

RNA editing occurs in all taxonomic groups of organisms, but increases dramatically in vertebrate, mammals and primates, with humans exhibiting the highest levels of edited and multiply-edited transcripts. RNA editing occurs in most, if not all tissues, but is particularly active in the nervous system, where transcripts encoding proteins involved in fast neural transmission, such as ion channels and ligand-gated receptors [1, 2]. These species-specific alterations have profound importance for normal nervous system function.

A to I editing is much more abundant in humans than in mice, and over 90 percent of this increased editing occurs in Alu elements in mainly noncoding regions of RNAs, i.e., in untranslated regions (UTRs) of mRNAs, in introns and intergenic transcripts.

All of this fits nicely with the use of Alu elements as a means of nudging the evolution of a human-like brain. I’ll probably talk about it all in more detail sometime in the future. But then things start to get really cool (but more speculative):

Learning and memory in the brain is similar to the immune response in many ways. A key feature of the immune system is the alteration of DNA sequence in the genome to generate receptor diversity, in part catalyzed by the APOBEC family of cytidine deaminases that can catalyze cytosine to uracil (C to U) and cytosine to thymine (C to T) editing of RNA and DNA.

The possibility exists that DNA recoding – rewriting genome DNA – is a central feature of both the immune and nervous systems. DNA recoding may be involved at the level of establishing neuronal identity and neuronal connectivity during development, learning and brain regeneration. And it appears that the brain, like the immune system, also changes according to experience.

Mattick and Mehler suggest that the potential recoding of DNA in nerve cells (and similarly in immune cells) might be primarily a mechanism whereby productive or learned changes induced by RNA editing are rewritten back to DNA via RNA-directed DNA repair. (See the latest model of RNA-directed recoding of DNA proposed for the immune system [5] by Ted Steele at Australian National University Canberra). This effectively fixes the altered genetic message once a particular neural circuitry and epigenetic state has been established.

The suggestion that there might be communication of RNA-encoded information back to the genome at the epigenetic and genetic levels would also potentially explain the surprising observation that diverse RNA species and associated regulatory signals are not only trafficked to the periphery of the nerve cell, but might also undergo retro-transport back to the nucleus. There is increasing evidence for retrograde transport of RNAs, including small RNAs, to the nucleus in a broad range of organisms, as well as for RNA informational exchange between cells through ‘exosomes’, specific RNA receptors and derivation of presynaptic RNA from surrounding glial cells.

BTW, if abiogenesis did occur and did involve an RNA World, a human-like brain was in the cards. Y’just can’t run from the Bunny!

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