ABSTRACT
The story of RNAi in fungi began with an interesting finding reported by Romano and Machino in 1992, whereby gene expression was shown to be interfered with by transformation with homologous sequences in the fungus Neurospora crassa (Romano and Machino, 1992). The gene inactivation was spontaneously reversible and involved the silencing of both transgenes and endogenous genes. This phenomenon was termed ‘quelling’. An intriguing feature of quelling is that it is dominant in heterokaryons with nuclei from quelled and wild-type strains, suggesting that a mobile signal acts in trans to cause silencing (Cogoni et al., 1996). A series of studies on quelling-deficient (qde) mutants of N. crassa (Cogoni and Macino, 1997) has provided evidence of the molecular link between quelling and RNAmediated gene-silencing mechanisms in other organisms, which include post-transcriptional gene silencing (PTGS) or co-suppression in plants and RNAi in animals. Moreover, the qde-1 mutant was shown to be defective in an RNA-dependent RNA polymerase (RdRP) (Cogoni and Macino, 1999), which is consistent with the findings that the SDE1/SGS2 gene in Arabidopsis (Dalmay et al., 2000; Mourrain et al., 2000) and ego-1 gene in Caenorhabditis elegans (Smardon et al., 2000), both of which encode RdRP, are required for PTGS and RNAi, respectively. Similarly, the protein product encoded by the second qde gene, qde-2, was shown to be a member of the Argonaute family, which is an essential component of the PTGS and RNAi pathways (Cogoni and Macino, 2000; Fagard et al., 2000). Furthermore, involvement of two dicer proteins (Dcl-1 and Dcl-2) and siRNA biogenesis in the quelling pathway was recently demonstrated (Catalanotto et al., 2002, 2004). Thus, the genetic and biochemical evidence suggests that quelling belongs to the broad category of RNA-mediated gene-silencing mechanisms, exemplified by RNAi, that are evolutionary conserved in most eukaryotes.
