PT  - JOURNAL ARTICLE
AU  - Ildar Gainetdinov
AU  - Cansu Colpan
AU  - Katharine Cecchini
AU  - Paul Albosta
AU  - Karina Jouravleva
AU  - Joel Vega-Badillo
AU  - Yongjin Lee
AU  - Deniz M. Özata
AU  - Phillip D. Zamore
TI  - Terminal Modification, Sequence, and Length Determine Small RNA Stability in Animals
AID  - 10.1101/2020.09.08.287979
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.08.287979
4099  - http://biorxiv.org/content/early/2020/09/08/2020.09.08.287979.short
4100  - http://biorxiv.org/content/early/2020/09/08/2020.09.08.287979.full
AB  - In animals, piRNAs, siRNAs, and miRNAs 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. Here, we report that trimming and methylation protect mouse piRNAs from different decay mechanisms. In the absence of 2′-O-methylation, mouse piRNAs with extensive complementarity to long RNAs become unstable. In flies, 2′-O-methylation similarly protects both piRNAs and siRNAs from complementarity-dependent destabilization. Animal miRNAs are unmethylated, and complementarity-dependent destabilization helps explain differences in miRNA decay rates in both mice and flies. In contrast, trimming protects mouse piRNAs from a separate degradation pathway unaffected by target complementarity but sensitive to the 3′ terminal, untrimmed sequence. Because distinct sets of mouse piRNAs are protected by each of these mechanisms, loss of both trimming and 2′-O-methylation causes the piRNA pathway to collapse, demonstrating that these two small RNA modifications collaborate to stabilize piRNAs.Highlights2′-O-methylation protects mouse and fly piRNAs from complementarity-dependent decay2′-O-methylation protects fly siRNAs with extensive complementarity to long RNAsComplementarity to long RNAs predicts the half-life of fly and mouse miRNAsMouse pre-piRNA decay reflects both pre-piRNA sequence and PIWI protein identityCompeting Interest StatementThe authors have declared no competing interest.