The diverse roles of RNA helicases in RNAi

Ambrus, Aaron M.; Frolov, Maxim V.

doi:10.4161/cc.8.21.9887

Cited by 23 publications

(20 citation statements)

References 47 publications

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“…However, it is already clear that the presence of a RNA helicase activity (unwinding or as adaptor proteins) is necessary for the correct functioning at different steps of the RNAi pathway. As it was proposed in several reports, there are a number of potential roles for RNA helicases in RNAi [66]. Our findings in the qPCR experiments during antigenic variation suggest that RNA helicases may participate in RNAi.…”

Section: Discussionsupporting

confidence: 79%

“…Importantly, Dicer expression was up regulated at very short times and was maintained for hours, while gAgo expression raised at later times, in accordance with their roles in the RNAi process [65]. Although there is an incomplete understanding of how RNA helicases are regulated, it is possible that they operate at different steps of the RNAi pathway or performing different roles [66]. …”

Section: Resultsmentioning

confidence: 99%

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Putative SF2 helicases of the early-branching eukaryote Giardia lamblia are involved in antigenic variation and parasite differentiation into cysts

et al. 2012

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BackgroundRegulation of surface antigenic variation in Giardia lamblia is controlled post-transcriptionally by an RNA-interference (RNAi) pathway that includes a Dicer-like bidentate RNase III (gDicer). This enzyme, however, lacks the RNA helicase domain present in Dicer enzymes from higher eukaryotes. The participation of several RNA helicases in practically all organisms in which RNAi was studied suggests that RNA helicases are potentially involved in antigenic variation, as well as during Giardia differentiation into cysts.ResultsAn extensive in silico analysis of the Giardia genome identified 32 putative Super Family 2 RNA helicases that contain almost all the conserved RNA helicase motifs. Phylogenetic studies and sequence analysis separated them into 22 DEAD-box, 6 DEAH-box and 4 Ski2p-box RNA helicases, some of which are homologs of well-characterized helicases from higher organisms. No Giardia putative helicase was found to have significant homology to the RNA helicase domain of Dicer enzymes. Additionally a series of up- and down-regulated putative RNA helicases were found during encystation and antigenic variation by qPCR experiments. Finally, we were able to recognize 14 additional putative helicases from three different families (RecQ family, Swi2/Snf2 and Rad3 family) that could be considered DNA helicases.ConclusionsThis is the first comprehensive analysis of the Super Family 2 helicases from the human intestinal parasite G. lamblia. The relative and variable expression of particular RNA helicases during both antigenic variation and encystation agrees with the proposed participation of these enzymes during both adaptive processes. The putatives RNA and DNA helicases identified in this early-branching eukaryote provide initial information regarding the biological role of these enzymes in cell adaptation and differentiation.

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Section: Discussionsupporting

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Putative SF2 helicases of the early-branching eukaryote Giardia lamblia are involved in antigenic variation and parasite differentiation into cysts

et al. 2012

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“…RNA helicases are ATP-dependent enzymes that unwind dsRNA, suggesting RnhA involvement in the separation of the two strands of the siRNAs and therefore a cooperative role with QIP and AGO proteins during the production of mature siRNAs. However, recent studies showed that the RNA helicase activity of these enzymes might not be required, and have suggested a more extensive function at every level of the RNAi pathway [32]. Our findings implicate RnhA in the production of epimutants in M .…”

Section: Discussionmentioning

confidence: 58%

A non-canonical RNA degradation pathway suppresses RNAi-dependent epimutations in the human fungal pathogen Mucor circinelloides

et al. 2017

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Mucorales are a group of basal fungi that includes the casual agents of the human emerging disease mucormycosis. Recent studies revealed that these pathogens activate an RNAi-based pathway to rapidly generate drug-resistant epimutant strains when exposed to stressful compounds such as the antifungal drug FK506. To elucidate the molecular mechanism of this epimutation pathway, we performed a genetic analysis in Mucor circinelloides that revealed an inhibitory role for the non-canonical RdRP-dependent Dicer-independent silencing pathway, which is an RNAi-based mechanism involved in mRNA degradation that was recently identified. Thus, mutations that specifically block the mRNA degradation pathway, such as those in the genes r3b2 and rdrp3, enhance the production of drug resistant epimutants, similar to the phenotype previously described for mutation of the gene rdrp1. Our genetic analysis also revealed two new specific components of the epimutation pathway related to the quelling induced protein (qip) and a Sad-3-like helicase (rnhA), as mutations in these genes prevented formation of drug-resistant epimutants. Remarkably, drug-resistant epimutant production was notably increased in M. circinelloides f. circinelloides isolates from humans or other animal hosts. The host-pathogen interaction could be a stressful environment in which the phenotypic plasticity provided by the epimutant pathway might provide an advantage for these strains. These results evoke a model whereby balanced regulation of two different RNAi pathways is determined by the activation of the RNAi-dependent epimutant pathway under stress conditions, or its repression when the regular maintenance of the mRNA degradation pathway operates under non-stress conditions.

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“…RNA helicases are well known players in sRNA metabolism in eukaryotic systems, having implications in cell development, viral infection and cancer 10 , 11 , 121 . It is therefore likely that RNA helicases perform a role in sRNA metabolism in prokaryotes.…”

Section: Rna Helicases In Translationmentioning

confidence: 99%

RNA helicases

Owttrim

2013

RNA Biology

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Similar to proteins, RNA molecules must fold into the correct conformation and associate with protein complexes in order to be functional within a cell. RNA helicases rearrange RNA secondary structure and RNA-protein interactions in an ATP-dependent reaction, performing crucial functions in all aspects of RNA metabolism. In prokaryotes, RNA helicase activity is associated with roles in housekeeping functions including RNA turnover, ribosome biogenesis, translation and small RNA metabolism. In addition, RNA helicase expression and/or activity are frequently altered during cellular response to abiotic stress, implying they perform defined roles during cellular adaptation to changes in the growth environment. Specifically, RNA helicases contribute to the formation of cold-adapted ribosomes and RNA degradosomes, implying a role in alleviation of RNA secondary structure stabilization at low temperature. A common emerging theme involves RNA helicases acting as scaffolds for protein-protein interaction and functioning as molecular clamps, holding RNA-protein complexes in specific conformations. This review highlights recent advances in DEAD-box RNA helicase association with cellular response to abiotic stress in prokaryotes.

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The diverse roles of RNA helicases in RNAi

Cited by 23 publications

References 47 publications

Putative SF2 helicases of the early-branching eukaryote Giardia lamblia are involved in antigenic variation and parasite differentiation into cysts

Putative SF2 helicases of the early-branching eukaryote Giardia lamblia are involved in antigenic variation and parasite differentiation into cysts

A non-canonical RNA degradation pathway suppresses RNAi-dependent epimutations in the human fungal pathogen Mucor circinelloides

RNA helicases

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