5guh
Crystal structure of silkworm PIWI-clade Argonaute Siwi bound to piRNA
Structural highlights
FunctionSIWI_BOMMO Endoribonuclease that plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (PubMed:19460866, PubMed:27693359). Plays an essential role in meiotic differentiation of spermatocytes, germ cell differentiation and in self-renewal of spermatogonial stem cells (PubMed:19460866, PubMed:25558067, PubMed:27693359). Its presence in oocytes suggests that it may participate in similar functions during oogenesis in females (PubMed:18191035). Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons (PubMed:19460866, PubMed:25558067, PubMed:27693359). Directly binds piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements (PubMed:19460866, PubMed:25558067, PubMed:27693359). Recognizes piRNAs containing a phosphate at the 5'-end and a 2'-O-methylation modification at the 3'-end (PubMed:27693359). Strongly prefers a uridine in the first position of their guide (g1U preference, also named 1U-bias) and a complementary adenosine in the target (t1A bias) (PubMed:24757166, PubMed:27693359). Plays a key role in the piRNA amplification loop, also named ping-pong amplification cycle: antisense piRNA-bound Siwi and sense piRNA-bound Ago3 reciprocally cleave complementary transcripts, to couple the amplification of piRNAs with the repression of transposable elements. In this process Siwi acts as a 'slicer-competent' piRNA endoribonuclease that cleaves primary piRNAs, which are then loaded onto Ago3 (PubMed:27693359). In this process, Siwi requires the RNA unwinding activity of the RNA helicase Vasa for the release of the cleavage products (PubMed:25558067).[1] [2] [3] [4] [5] Publication Abstract from PubMedPIWI-clade Argonaute proteins associate with PIWI-interacting RNAs (piRNAs) and silence transposable elements in animal gonads. Here, we report the crystal structure of a silkworm PIWI-clade Argonaute, Siwi, bound to the endogenous piRNA, at 2.4 A resolution. Siwi adopts a bilobed architecture consisting of N-PAZ and MID-PIWI lobes, in which the 5' and 3' ends of the bound piRNA are anchored by the MID-PIWI and PAZ domains, respectively. A structural comparison of Siwi with AGO-clade Argonautes reveals notable differences in their nucleic-acid-binding channels, likely reflecting the distinct lengths of their guide RNAs and their mechanistic differences in guide RNA loading and cleavage product release. In addition, the structure reveals that Siwi and prokaryotic, but not eukaryotic, AGO-clade Argonautes share unexpected similarities, such as metal-dependent 5'-phosphate recognition and a potential structural transition during the catalytic-tetrad formation. Overall, this study provides a critical starting point toward a mechanistic understanding of piRNA-mediated transposon silencing. Crystal Structure of Silkworm PIWI-Clade Argonaute Siwi Bound to piRNA.,Matsumoto N, Nishimasu H, Sakakibara K, Nishida KM, Hirano T, Ishitani R, Siomi H, Siomi MC, Nureki O Cell. 2016 Oct 6;167(2):484-497.e9. doi: 10.1016/j.cell.2016.09.002. Epub 2016, Sep 29. PMID:27693359[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
