The TDRD5/7-like protein, LOTR-1, functions within Z granules to balance epigenetic signals in the Caenorhabditis elegans germline

ABSTRACT: LOTUS and Tudor domain containing proteins have critical roles in the germline. Proteins that contain these domains, such as Tejas/Tapas in Drosophila, help localize Vasa to the germ granules and facilitate piRNA transposon mediated silencing. The homologous proteins in mammals, TDRD5 and TDRD7, are required during spermiogenesis. Until now, LOTUS + Tudor domain proteins in C. elegans have remained elusive. Here we describe LOTR-1 (D1081.7), which derives its name from its LOTUS and Tudor domains. Interestingly, LOTR-1 docks next to P granules to colocalize with the Z-granule component ZNFX-1. LOTR-1’s Z-granule association requires its Tudor domain, but both LOTUS and Tudor deletions affect brood size when coupled with a knockdown of the Vasa homolog glh-1. LOTR-1 IP-mass spectrometry confirmed a Tudor-dependent association with Z-granule proteins ZNFX-1 and WAGO-1, but also with germ-granule proteins DEPS-1, the piRNA Argonaute PRG-1, and other WAGO-class Argonautes. Like znfx-1, lotr-1 mutants redistribute the coverage of 22G-RNAs toward the 5’ end of mutator targets and impact transgenerational epigenetic inheritance. Unlike znfx-1, the 5’ shift in 22G-RNA coverage does not extend to CSR-1 targets. Combined, these results suggest that LOTR-1 facilitates interactions between PRG-1/WAGO-class Argonautes, ZNFX-1 and target 3’UTRs to balance 22G-RNA distribution across mutator targets.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Caenorhabditis Elegans

SUBMITTER: F Butter  

LAB HEAD: Falk Butter

PROVIDER: PXD025186 | Pride | 2022-05-28

REPOSITORIES: Pride