ZSP‐1 is a Z granule surface protein required for Z granule fluidity and germline immortality in Caenorhabditis elegans

Abstract

Germ granules are biomolecular condensates that form in germ cells of all/most animals, where they regulate mRNA expression to promote germ cell function and totipotency. In the adult Caenorhabditis elegans germ cell, these granules are composed of at least four distinct sub-compartments, one of which is the Z granule. To better understand the role of the Z granule in germ cell biology, we conducted a genetic screen for genes specifically required for Z granule assembly or morphology. Here, we show that zsp-1, which encodes a low-complexity/polyampholyte-domain protein, is required for Z granule homeostasis. ZSP-1 localizes to the outer surface of Z granules. In the absence of ZSP-1, Z granules swell to an abnormal size, fail to segregate with germline blastomeres during development, and lose their liquid-like character. Finally, ZSP-1 promotes piRNA-and siRNA-directed gene regulation and germline immortality. Our data suggest that Z granules coordinate small RNA-based gene regulation to promote germ cell function and that ZSP-1 helps/is need to maintain Z granule morphology and liquidity.

Intrinsically disordered protein PID‐2 modulates Z granules and is required for heritable piRNA‐induced silencing in theCaenorhabditis elegansembryo

“…Unfortunately, the direct assessment of colocalization between ZNFX‐1 and PID‐2 was thus far hampered by the very close linkage between the PID‐2::eGFP transgene and an available endogenously tagged ZNFX‐1 allele (Wan et al , 2018). Given that Wan et al (2020) show that PID‐2 (named ZSP‐1 by Wan et al) is indeed in Z granules, we did not further pursue PID‐2‐ZNFX‐1 colocalization ourselves.…”

Higher-order organization of biomolecular condensates

“…The zsp-1 gene is translated in the germline of C. elegans and forms puncta around the germ cell nuclei. Upon more detailed characterization of ZSP-1 localization using stimulated emission depletion microscopy, the authors found that ZSP-1 localized to the exterior of Z granules [ 204 ]. Moreover, proper ZSP-1 localization is critical for maintaining the liquid-like properties of the Z granule.…”

“…Interestingly, this finding is reminiscent of the internal organization of P granules, one of the three components in PZM complex. However, ZSP-1 and the P granule surface protein, MEG-3 have very different relationships with their respective condensates [ 84 , 116 , 204 ]. Nevertheless, in future studies, it will be of interest to determine if ZSP-1 and the P granule surface protein, MEG-3, interact in a bridge or node-based network, and whether this network is involved in TEI.…”

The Caenorhabditis elegans TDRD5/7-like protein, LOTR-1, interacts with the helicase ZNFX-1 to balance epigenetic signals in the germline

“…PID-2/4/5 are recently identified factors that affect the structure of Z granules, are required for germ cell immortality, and are similarly required to balance 22G-RNA signals. [38,39] These studies demonstrate a link between Z granules and the biogenesis and inheritance of 22G-RNAs.…”

“…[36] Known sub-granules include Z-granules, SIMR foci, and Mutator foci -each containing sets of proteins that refine and resolve processes or steps of small RNA biosynthesis. [37][38][39] C. elegans expresses several classes of small RNAs. [40,41] 21U-RNAs are considered the piRNAs of C. elegans due to their interaction with the germline-expressed PRG-1 Argonaute, the main Piwi-class Argonaute of C. elegans.…”