| First Author | Gainetdinov I | Year | 2021 |
| Journal | Mol Cell | Volume | 81 |
| Issue | 23 | Pages | 4826-4842.e8 |
| PubMed ID | 34626567 | Mgi Jnum | J:316804 |
| Mgi Id | MGI:6831145 | Doi | 10.1016/j.molcel.2021.09.012 |
| Citation | Gainetdinov I, et al. (2021) Terminal modification, sequence, length, and PIWI-protein identity determine piRNA stability. Mol Cell 81(23):4826-4842.e8 |
| abstractText | 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. |
