Journal Article

DZNE-2024-01339

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png An architectural role of specific RNA-RNA interactions in oskar granules.

Bose, M. ; Rankovic, B. (First author)DZNE* ; Mahamid, J. ; Ephrussi, A.

2024
Nature America New York, NY

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Please use a persistent id in citations: doi:10.1038/s41556-024-01519-3

Abstract: Ribonucleoprotein (RNP) granules are membraneless condensates that organize the intracellular space by compartmentalization of specific RNAs and proteins. Studies have shown that RNA tunes the phase behaviour of RNA-binding proteins, but the role of intermolecular RNA-RNA interactions in RNP granules in vivo remains less explored. Here we determine the role of a sequence-specific RNA-RNA kissing-loop interaction in assembly of mesoscale oskar RNP granules in the female Drosophila germline. We show that a two-nucleotide mutation that disrupts kissing-loop-mediated oskar messenger RNA dimerization impairs condensate formation in vitro and oskar granule assembly in the developing oocyte, leading to defective posterior localization of the RNA and abrogation of oskar-associated processing bodies upon nutritional stress. This specific trans RNA-RNA interaction acts synergistically with the scaffold RNA-binding protein, Bruno, in driving condensate assembly. Our study highlights the architectural contribution of an mRNA and its specific secondary structure and tertiary interactions to the formation of an RNP granule that is essential for embryonic development.

Keyword(s): Animals (MeSH) ; Drosophila Proteins: metabolism (MeSH) ; Drosophila Proteins: genetics (MeSH) ; Drosophila melanogaster: metabolism (MeSH) ; Drosophila melanogaster: genetics (MeSH) ; RNA-Binding Proteins: metabolism (MeSH) ; RNA-Binding Proteins: genetics (MeSH) ; Female (MeSH) ; Oocytes: metabolism (MeSH) ; Ribonucleoproteins: metabolism (MeSH) ; Ribonucleoproteins: genetics (MeSH) ; RNA, Messenger: metabolism (MeSH) ; RNA, Messenger: genetics (MeSH) ; Cytoplasmic Granules: metabolism (MeSH) ; Mutation (MeSH) ; Drosophila Proteins ; osk protein, Drosophila ; RNA-Binding Proteins ; Ribonucleoproteins ; RNA, Messenger ; bru1 protein, Drosophila

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Contributing Institute(s):

1. Molecular Neuroscience (AG Milovanovic (Berlin))

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2024

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