RNA-mediated Transgenerational Epigenetic Inheritance of DNA Rearrangements and Copy Number

RNA, normally thought of as a conduit in gene expression, has a novel mode of action in some single-celled protozoa. This opportunity for RNA-mediated epigenetic inheritance is especially profound in the ciliate Oxytricha, which deletes 95% of its germline genome through global DNA rearrangements.  These events shatter its germline chromosomes and then sort and reorder the hundreds of thousands of pieces remaining. Maternally-inherited long, non-coding RNAs provide 1) instructions for sequence reordering, 2) a template for RNA-guided DNA repair that can transmit somatic mutations to the next generation (Nature 2008,  451:153-8), and 3) information to regulate DNA and chromosome copy number (PNAS 2010, 107:22140-4). The mechanism for all of these actions bypasses the traditional mode of inheritance via DNA, hinting at the power of RNA molecules to sculpt genomic information. This suggests that Oxytricha's somatic genome is truly an epigenome, formed through templates and signals arising from the previous generation, and offering a mechanism for the stable inheritance of acquired, spontaneous somatic substitutions, without altering the germline.