Sixteen Years of Meiotic Silencing by Unpaired DNA

The filamentous fungus Neurospora crassa possesses a process called meiotic silencing by unpaired DNA (MSUD). MSUD has a remarkable ability to scan homologous chromosomes for unpaired DNA during meiosis. After unpaired DNA is identified, MSUD silences all RNA from the unpaired DNA along with any RNA transcribed from homologous sequences at other locations in the genome, regardless of their pairing state. The mechanism by which unpaired DNA is detected is unknown. Unpaired DNA segments can be as short as 1.3kb, if not shorter, and DNA sequences with only a small level of polymorphism (6%) can be considered unpaired by MSUD. MSUD research has identified nine proteins required for full efficiency of the process, three of which are homologs of the canonical RNA interference (RNAi) proteins Dicer, Argonaute, and RNA-dependent RNA polymerase. Most MSUD proteins, including the RNAi homologs, appear to dock outside of the nuclear envelope during early stages of meiosis. Only two have been observed inside the nucleus, a low number given that the identification of unpaired DNA and the triggering of silencing must begin within this location. These two proteins may participate in the unpaired DNA detection process. Recent evidence indicates that the search for unpaired DNA is spatially constrained, possibly because of restrictions on the arrangement of chromatin loops during or after homolog pairing. This review attempts to provide a complete analysis of past, present, and future directions of MSUD research, starting with its discovery during a search for a conserved regulator of fungal development and ending with some benefits the process may provide to MSUD capable organisms.