@article{bc851b3edde1492bb1899b3b2dbc6d35,
title = "Terminal modification, sequence, length, and PIWI-protein identity determine piRNA stability",
abstract = "In 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.",
keywords = "2'-O-methylation, piRNA, PIWI, piwi-interacting RNA, RNA stability, RNA turnover, siRNA, small interfering RNA, small RNA, target-directed microRNA degradation",
author = "Ildar Gainetdinov and Cansu Colpan and Katharine Cecchini and Amena Arif and Karina Jouravleva and Paul Albosta and Joel Vega-Badillo and Yongjin Lee and {\"O}zata, {Deniz M.} and Zamore, {Phillip D.}",
note = "Funding Information: We thank the UMass Flow Cytometry Core Facility for help sorting mouse germ cells; the UMass Transgenic Animal Modeling Core for help generating Pnldc1em1Pdz/em1Pdz and Henmt1em1Pdz/em1Pdz mice; members of the Zamore and Mello laboratories for discussions and critical comments on the manuscript; Dimas Echeverria Moreno, Matthew R. Hassler, and Jacquelyn Sousa from the Khvorova laboratory for technical assistance; and Alex Bortvin for the anti-mouse LINE-1 ORF1p antibody. This work was supported in part by National Institutes of Health grants GM65236 and P01HD078253 to P.D.Z, and 1S10 OD028576 to the UMass Flow Cytometry Core Facility. Conceptualization, I.G. and P.D.Z.; methodology, I.G. C.C, K.J. A.A. and P.D.Z.; software, I.G.; investigation, I.G. C.C. K.C. A.A. P.A. J.V.-B. Y.L. and D.M.O.; formal analysis, I.G.; writing – original draft, C.C. I.G. and P.D.Z.; writing – review & editing, I.G. and P.D.Z.; funding acquisition, P.D.Z. P.D.Z. is a member of the editorial board of Molecular Cell. One or more of the authors of this paper self-identifies as a member of the LGBTQ+ community. Funding Information: We thank the UMass Flow Cytometry Core Facility for help sorting mouse germ cells; the UMass Transgenic Animal Modeling Core for help generating Pnldc1 em1Pdz/em1Pdz and Henmt1 em1Pdz/em1Pdz mice; members of the Zamore and Mello laboratories for discussions and critical comments on the manuscript; Dimas Echeverria Moreno, Matthew R. Hassler, and Jacquelyn Sousa from the Khvorova laboratory for technical assistance; and Alex Bortvin for the anti-mouse LINE-1 ORF1p antibody. This work was supported in part by National Institutes of Health grants GM65236 and P01HD078253 to P.D.Z, and 1S10 OD028576 to the UMass Flow Cytometry Core Facility. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = dec,
day = "2",
doi = "10.1016/j.molcel.2021.09.012",
language = "English (US)",
volume = "81",
pages = "4826--4842.e8",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "23",
}