Terminal modification, sequence, length, and PIWI-protein identity determine piRNA stability
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Özata, Deniz M
Zamore, Phillip D
UMass Chan AffiliationsRNA Therapeutics Institute
Document TypeJournal Article
small interfering RNA
target-directed microRNA degradation
MetadataShow full item record
AbstractIn animals, PIWI-interacting RNAs (piRNAs) silence transposons, fight viral infections, and regulate gene expression. piRNA biogenesis concludes with 3' terminal trimming and 2'-O-methylation. Both trimming and methylation influence piRNA stability. Our biochemical data show that multiple mechanisms destabilize unmethylated mouse piRNAs, depending on whether the piRNA 5' or 3' sequence is complementary to a trigger RNA. Unlike target-directed degradation of microRNAs, complementarity-dependent destabilization of piRNAs in mice and flies is blocked by 3' terminal 2'-O-methylation and does not require base pairing to both the piRNA seed and the 3' sequence. In flies, 2'-O-methylation also protects small interfering RNAs (siRNAs) from complementarity-dependent destruction. By contrast, pre-piRNA trimming protects mouse piRNAs from a degradation pathway unaffected by trigger complementarity. In testis lysate and in vivo, internal or 3' terminal uridine- or guanine-rich tracts accelerate pre-piRNA decay. Loss of both trimming and 2'-O-methylation causes the mouse piRNA pathway to collapse, demonstrating that these modifications collaborate to stabilize piRNAs.
SourceGainetdinov I, Colpan C, Cecchini K, Arif A, Jouravleva K, Albosta P, Vega-Badillo J, Lee Y, Özata DM, Zamore PD. Terminal modification, sequence, length, and PIWI-protein identity determine piRNA stability. Mol Cell. 2021 Dec 2;81(23):4826-4842.e8. doi: 10.1016/j.molcel.2021.09.012. Epub 2021 Oct 8. PMID: 34626567; PMCID: PMC8642287.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/51981
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