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A Non-canonical RNA Silencing Pathway Promotes mRNA Degradation in Basal Fungi


Most eukaryotic organisms produce different classes of endogenous small RNA (esRNA) molecules that suppress gene expression through RNA interference (RNAi) pathways. These pathways, which may differ among organisms, are normally involved in genome defense, heterochromatin formation and regulation of genes involved in multiple cellular functions. In the basal fungus Mucor circinelloides, an opportunistic human pathogen, we previously demonstrated that biogenesis of a large group of esRNA molecules requires a basic RNAi machinery consisting of a Dicer-like protein, an Argonaute nuclease and two RNA-dependent RNA polymerases. This canonical dicer-dependent pathway regulates different cellular processes, such as vegetative sporulation. Besides those esRNAs generated by this canonical RNAi pathway, we have identified a new rdrp-dependent dicer-independent esRNA class. These esRNAs are produced by a degradation pathway in which the RdRP proteins signal specific transcripts that will be degraded by a newly identified RNase. This RNase, named R3B2, presents unique domain architecture, can only be found in basal fungi and it is also involved in the canonical dicer-dependent RNAi pathway. Our results expand the role of RdRPs in gene silencing and reveal the involvement of these proteins in a new RNA degradation process that could represent the first step in the evolution of RNAi.


Vyšlo v časopise: A Non-canonical RNA Silencing Pathway Promotes mRNA Degradation in Basal Fungi. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005168
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005168

Souhrn

Most eukaryotic organisms produce different classes of endogenous small RNA (esRNA) molecules that suppress gene expression through RNA interference (RNAi) pathways. These pathways, which may differ among organisms, are normally involved in genome defense, heterochromatin formation and regulation of genes involved in multiple cellular functions. In the basal fungus Mucor circinelloides, an opportunistic human pathogen, we previously demonstrated that biogenesis of a large group of esRNA molecules requires a basic RNAi machinery consisting of a Dicer-like protein, an Argonaute nuclease and two RNA-dependent RNA polymerases. This canonical dicer-dependent pathway regulates different cellular processes, such as vegetative sporulation. Besides those esRNAs generated by this canonical RNAi pathway, we have identified a new rdrp-dependent dicer-independent esRNA class. These esRNAs are produced by a degradation pathway in which the RdRP proteins signal specific transcripts that will be degraded by a newly identified RNase. This RNase, named R3B2, presents unique domain architecture, can only be found in basal fungi and it is also involved in the canonical dicer-dependent RNAi pathway. Our results expand the role of RdRPs in gene silencing and reveal the involvement of these proteins in a new RNA degradation process that could represent the first step in the evolution of RNAi.


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