How do RNA molecules distinguish self from non-self?

Abstract

RNA molecules form homotypic clusters in a variety of contexts. mRNAs enriched in germ granules in <i>Drosophila</i> embryos are a canonical example, with <i>polar granule component</i> (<i>pgc</i>) mRNAs colocalized with other <i>pgc</i> mRNAs, and <i>nanos</i> mRNAs with other <i>nanos</i> mRNAs. The observation of homotypic clustering poses a conundrum: how can RNAs of a given sequence distinguish other RNAs of the same sequence from those with different sequences? Here we show in silico that RNAs can distinguish self from non-self through the presence of palindromic regions within RNA sequences, and that palindromes can mediate homotypic clustering. We further show that RNA-RNA interactions are unlikely to lead to homotypic clusters in the absence of palindromes due to a competition between intra- and intermolecular RNA structures. We explore the implications of the palindrome-based clustering hypothesis for <i>nanos</i> and <i>pgc</i> mRNAs, and suggest how it may clear up a surprising feature of <i>nanos</i> clusters. More broadly, our results indicate that the palindrome content of RNAs may be under evolutionary selection pressure across a range of contexts.