We're going to start this lecture by returning to some of the aspects already mentioned, through the question of the regulatory role of non-coding RNAs (ncRNAs) in DNA repair. I will do so with greater emphasis on NHEJ, since neuronal longevity is primarily aimed at post-mitotic cells (although HR will sometimes have something to say about this). The purpose of DIA III.2 is simply to remind you of the two repair pathways for double-strand breaks, the NHEJ pathway (left) and the HR pathway (right). For NHEJ, the sequence of events is now familiar, with Ku70 and Ku80 covering the ends released by the break and mobilizing the various phosphorylation enzymes, including DNA-PKCs, which in turn phosphorylate Artemis, leading to the generation of overlapping ends and then to repair by the combined action of DNA-polymerases, which fill the holes, and ligases, which bind everything together.
I don't really need to dwell too much on non-coding RNAs, since we've often talked about them in previous years. For newcomers, however, or those who may have forgotten, I'll remind you that regulatory domains (which don't code for proteins) account for around 98% of the genome, and that non-coding RNAs are the most numerous products of these regulatory regions. These RNAs are transcribed from DNA but do not code for proteins, thus disobeying the classic, but over-simplifying and dogmatic, schema of the temporal and unidirectional DNA-RNA-Protein sequence (I remind you that we can also switch from RNA to DNA, as we saw in connection with retrotransposition and as we'll see again when we talk about telomeres on November 4th of this year. These non-coding RNAs have numerous biological functions in the regulation of gene expression, at all levels: transcription (DNA gives rise to RNA), splicing (the same primary transcript can give rise to several distinct mRNAs), RNA transport (translation of RNAs into proteins can take place locally after RNA transport, as in the case of perimitochondrial messenger RNAs or RNAs present in the synapse and "on hold"). To this must be added the function of regulating the stability of messenger RNAs and their translation into proteins. These regulatory functions may or may not be associated with mechanisms for regulating genome stability, as in the case of piRNAs, which repress retrotransposon transcription. I won't go into this now, as we've already talked about it a lot, and we'll come back to it later in this lecture.
