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The profile of snoRNA-derived microRNAs that regulate expression of variant surface proteins in Giardia lamblia.
Cell Microbiol. 2012 May 9
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25 Jun 2012
Interesting Hypothesis, New Finding
DOI: 10.3410/f.716997866.792302871
Over the last five years the Wang lab has systematically dissected the origins and roles of microRNAs (miRNAs) in the protozoan Giardia lamblia. In a series of previous publications they have reported on the potential role of small nucleolar RNA (snoRNA)-derived miRNAs in the regulation of variant-surface...Continue reading
Over the last five years the Wang lab has systematically dissected the origins and roles of microRNAs (miRNAs) in the protozoan Giardia lamblia. In a series of previous publications they have reported on the potential role of small nucleolar RNA (snoRNA)-derived miRNAs in the regulation of variant-surface protein (VSP) expression in this parasite {1-3}. Only one of the 220 annotated VSP genes is expressed in a Giardia trophozoite at any one time, but cells can undergo antigenic variation, i.e. periodic switching to the expression of a different VSP. Although there is consensus about the post-transcriptional nature of VSP expression regulation, the mechanism by which mRNA of only one VSP variant is translated is controversial. In this paper the authors analyzed the potential of 21 identified snoRNAs in the protozoan parasite Giardia to act as precursors of miRNAs. Two novel miRNAs (MiR6 and MiR10) were also identified along with numerous target sites in the 3'ends of VSP mRNAs. In a series of carefully executed in silico and quantitative in vitro experiments the authors show direct evidence for miRNA-dependent regulation of VSP expression. They also demonstrate that the large majority of VSP mRNAs harbor one or several target sequences for the currently known miRNAs. Although the mechanism by which the Giardia cell controls repression of all but one VSP variant through miRNA binding remains to be discovered, this paper is an important milestone on the way to unravelling the machinery governing antigenic variation and presumably other regulated pathways in Giardia.
References
1.
A microRNA derived from an apparent canonical biogenesis pathway regulates variant surface protein gene expression in Giardia lamblia.
RNA. 2011 Dec; 17(12): 2152-64
PMID: 22033329
DOI: 10.1261/rna.028118.111
2.
Gene regulation in Giardia lambia involves a putative microRNA derived from a small nucleolar RNA.
PLoS Negl Trop Dis. 2011 Oct; 5(10): e1338
PMID: 22028939
DOI: 10.1371/journal.pntd.0001338
3.
snoRNA, a novel precursor of microRNA in Giardia lamblia.
PLoS Pathog. 2008 Nov; 4(11): e1000224
PMID: 19043559
DOI: 10.1371/journal.ppat.1000224
Disclosures
None declared
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Hehl A: F1000Prime Recommendation of [Li W et al., Cell Microbiol 2012]. In F1000Prime, 25 Jun 2012; DOI: 10.3410/f.716997866.792302871. F1000Prime.com/716997866#eval792302871
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In the current investigation, we analysed all the known small nucleolar RNAs (snoRNAs) in the deeply branching protozoan parasite Giardia lamblia for potential microRNAs (miRNAs) that might be derived from them. Two putative miRNAs have since been identified by Northern blot, primer extension, 3' RACE and co-immunoprecipitation with Giardia Argonaute (GlAgo), and designated miR6 and miR10. Giardia Dicer (GlDcr) is capable of processing the snoRNAs into the corresponding miRNAs in vitro. Potential miR6 and miR10 binding sites in Giardia genome were predicted bio-informatically. A miR6 binding site was found at the 3' untranslated regions (UTR) of 44 variant surface protein (vsp) genes, whereas a miR10 binding site was identified at the 3' end of 159 vsp open-reading frames. Thirty-three of these vsp genes turned out to contain binding sites for both miR6 and miR10. A reporter mRNA tagged with the 3' end of vsp1267, which contains the target sites for both miRNAs, was translationally repressed by both miRNAs in Giardia. Episomal expression of an N-terminal c-myc tagged VSP1267 was found significantly repressed by introducing either miR6 or miR10 into the cells and the repressive effects were additive. When the 2'-O-methyl antisense oligos (ASOs) of either miR6 or miR10 was introduced, however, there was an enhancement of tagged VSP1267 expression suggesting an inhibition of the repressive effects of endogenous miR6 or miR10 by the ASOs. Of the total 220 vsp genes in Giardia, we have now found 178 of them carrying putative binding sites for all the miRNAs that have been currently identified, suggesting that miRNAsare likely the regulators of VSP expression in Giardia.
© 2012 Blackwell Publishing Ltd.
DOI: 10.1111/j.1462-5822.2012.01811.x
PMID: 22568619
