Antagonistic interactions among structured domains in the multivalent Bicc1-ANKS3-ANKS6 protein network govern phase transitioning of target mRNAs.

Biological sciences Biomolecules Protein

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
16 Jun 2023
Historique:
received: 16 12 2022
revised: 11 04 2023
accepted: 05 05 2023
medline: 5 6 2023
pubmed: 5 6 2023
entrez: 5 6 2023
Statut: epublish

Résumé

The growing number of diseases linked to aberrant phase transitioning of ribonucleoproteins highlights the need to uncover how the interplay between multivalent protein and RNA interactions is regulated. Cytoplasmic granules of the RNA binding protein Bicaudal-C (Bicc1) are regulated by the ciliopathy proteins ankyrin (ANK) and sterile alpha motif (SAM) domain-containing ANKS3 and ANKS6, but whether and how target mRNAs are affected is unknown. Here, we show that head-to-tail polymers of Bicc1 nucleated by its SAM domain are interconnected by K homology (KH) domains in a protein meshwork that mediates liquid-to-gel transitioning of client transcripts. Moreover, while the dispersion of these granules by ANKS3 concomitantly released bound mRNAs, co-recruitment of ANKS6 by ANKS3 reinstated Bicc1 condensation and ribonucleoparticle assembly. RNA-independent Bicc1 polymerization and its dual regulation by ANKS3 and ANKS6 represent a new mechanism to couple the reversible immobilization of client mRNAs to controlled protein phase transitioning between distinct metastable states.

Identifiants

pubmed: 37275520
doi: 10.1016/j.isci.2023.106855
pii: S2589-0042(23)00932-X
pmc: PMC10232731
doi:

Types de publication

Journal Article

Langues

eng

Pagination

106855

Informations de copyright

© 2023 The Author(s).

Déclaration de conflit d'intérêts

The authors declare no competing interests.

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Auteurs

Benjamin Rothé (B)

Ecole Polytechnique Fédérale de Lausanne (EPFL) SV ISREC, Station 19, 1015 Lausanne, Switzerland.

Simon Fortier (S)

Ecole Polytechnique Fédérale de Lausanne (EPFL) SV ISREC, Station 19, 1015 Lausanne, Switzerland.

Céline Gagnieux (C)

Ecole Polytechnique Fédérale de Lausanne (EPFL) SV ISREC, Station 19, 1015 Lausanne, Switzerland.

Céline Schmuziger (C)

Ecole Polytechnique Fédérale de Lausanne (EPFL) SV ISREC, Station 19, 1015 Lausanne, Switzerland.

Daniel B Constam (DB)

Ecole Polytechnique Fédérale de Lausanne (EPFL) SV ISREC, Station 19, 1015 Lausanne, Switzerland.

Classifications MeSH