Small RNAs and Programmed Genome Rearrangement

The sea lamprey (Petromyzon marinus) undergoes programmed genome rearrangements (PGRs) during embryogenesis that results in the deletion of ~0.5 Gb of germline DNA from the somatic lineage. Previous analyses have shown that hundreds of genes with a strong potential for antagonistic pleiotropic interactions are removed from somatic tissue but maintained in germline. Previous studies have shown that small-noncoding-RNAs (snRNAs) are responsible for guiding cellular machinery to recombination sites during programmed rearrangement of ciliate genomes. In particular, homologs of germline specific piwi-interacting RNAs (piRNAs) control which sequences are retained in a sequence specific manner. Additionally, in vertebrates, micro-RNAs (miRNAs) have been shown to act as major regulators of early gene expression. Thus we hypothesized that snRNAs might affect targeting of programmed deletions or be targets of deletion. As such, we sought to characterize the snRNA pool in rearranging developing lamprey embryos.

Deep sequencing of rearranging embryos has identified >100 piRNA and >180 miRNA candidate loci that appear to be removed from the somatic lineage and maintained in the germline. Elimination of genes such as miR-30 (an oncogenic factor), suggests a common underlying logic for elimination of snRNAs and coding regions. The observation that hundreds of candidate piRNAs are eliminated mirrors the PGR process in ciliates, which could implicate piRNAs as a convergent epigenetic signal for sequence deletion. Future experiments will provide insight into the exact function of snRNAs during early development of this basal vertebrate, and could potentially lead to descriptions of similar pathways operating in higher vertebrates, including humans.