PIWI proteins use PIWI-interacting RNAs (piRNAs) to identify and silence transposable elements and thereby maintain genome integrity between metazoan generations. The targeting of transposable elements by PIWI has been compared to mRNA target recognition by Argonaute proteins, which use microRNA (miRNA) guides, but the extent to which piRNAs resemble miRNAs is not known. Here we present cryo-electron microscopy structures of a PIWI-piRNA complex from the sponge Ephydatia fluviatilis with and without target RNAs, and a biochemical analysis of target recognition. Mirroring Argonaute, PIWI identifies targets using the piRNA seed region. However, PIWI creates a much weaker seed so that stable target association requires further piRNA-target pairing, making piRNAs less promiscuous than miRNAs. Beyond the seed, the structure of PIWI facilitates piRNA-target pairing in a manner that is tolerant of mismatches, leading to long-lived PIWI-piRNA-target interactions that may accumulate on transposable-element transcripts. PIWI ensures targeting fidelity by physically blocking the propagation of piRNA-target interactions in the absence of faithful seed pairing, and by requiring an extended piRNA-target duplex to reach an endonucleolytically active conformation. PIWI proteins thereby minimize off-targeting cellular mRNAs while defending against evolving genomic threats.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302021 | PMC |
http://dx.doi.org/10.1038/s41586-021-03856-x | DOI Listing |
Exp Eye Res
January 2025
Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, 605 014, India. Electronic address:
Diabetic Retinopathy (DR), a leading complication of diabetes mellitus, has long been considered as a microvascular disease of the retina. However, recent evidence suggests that DR is a neurovascular disease, characterized by the degeneration of retinal neural tissue and microvascular abnormalities encompassing ischemia, neovascularization, and blood-retinal barrier breakdown, ultimately leading to blindness. The intricate relationship between the retina and vascular cells constitutes a neurovascular unit, a multi-cellular framework of retinal neurons, glial cells, immune cells, and vascular cells, which facilitates neurovascular coupling, linking neuronal activity to blood flow.
View Article and Find Full Text PDFSci Data
January 2025
Gakushuin University, Faculty of Science, Department of Life Science, Mejiro 1-5-1, Toshima-ku, Tokyo, 171-8588, Japan.
The wild silk moth, Bombyx mandarina, is the closest relative of the domesticated silk moth, Bombyx mori. National BioResource Project of Japan (NBRP) maintains a B. mandarina strain derived from individuals captured at Sakado (Saitama, Japan) in 1982.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
From RNA interference to chromatin silencing, diverse genome defense pathways silence selfish genetic elements to safeguard genome integrity. Despite their diversity, different defense pathways share a modular organization, where numerous specificity factors identify diverse targets and common effectors silence them. In the PIWI-interacting RNA (piRNA) pathway, target RNAs are first identified by complementary base pairing with piRNAs and then silenced by PIWI-clade nucleases.
View Article and Find Full Text PDFThe activation of progenitor cells near wound sites is a common feature of regeneration across species, but the conserved signaling mechanisms responsible for this step in whole-body regeneration are still incompletely understood. The acoel undergoes whole-body regeneration using Piwi+ pluripotent adult stem cells (neoblasts) that accumulate at amputation sites early in the regeneration process. The EGFR signaling pathway has broad roles in controlling proliferation, migration, differentiation, and cell survival across metazoans.
View Article and Find Full Text PDFFEBS J
December 2024
Laboratory of Germline Biology, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
Discovered two decades ago, PIWI-interacting RNAs (piRNAs) are crucial for silencing transposable elements (TEs) in animal gonads, thereby protecting the germline genome from harmful transposition, and ensuring species continuity. Silencing of TEs is achieved through transcriptional and post-transcriptional suppression by piRNAs and the PIWI clade of Argonaute proteins within non-membrane structured organelle. These structures are composed of proteins involved in piRNA processing, including PIWIs and other proteins by distinct functional motifs such as the Tudor domain, LOTUS, and intrinsic disordered regions (IDRs).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!