Details

Autor(en) / Beteiligte

• Benjamin Rothé
• Yayoi Ikawa
• Zhidian Zhang
• Takanobu A Katoh
• Eriko Kajikawa
• Katsura Minegishi
• Sai Xiaorei
• Simon Fortier
• Matteo Dal Peraro
• Hiroshi Hamada
• Daniel B Constam

Titel

Bicc1 ribonucleoprotein complexes specifying organ laterality are licensed by ANKS6-induced structural remodeling of associated ANKS3

Ist Teil von

• PLoS biology, 2023-09, Vol.21 (9), p.e3002302

Ort / Verlag

Public Library of Science (PLoS)

Erscheinungsjahr

2023

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Organ laterality of vertebrates is specified by accelerated asymmetric decay of Dand5 mRNA mediated by Bicaudal-C1 (Bicc1) on the left side, but whether binding of this or any other mRNA to Bicc1 can be regulated is unknown. Here, we found that a CRISPR-engineered truncation in ankyrin and sterile alpha motif (SAM)-containing 3 (ANKS3) leads to symmetric mRNA decay mediated by the Bicc1-interacting Dand5 3' UTR. AlphaFold structure predictions of protein complexes and their biochemical validation by in vitro reconstitution reveal a novel interaction of the C-terminal coiled coil domain of ANKS3 with Bicc1 that inhibits binding of target mRNAs, depending on the conformation of ANKS3 and its regulation by ANKS6. The dual regulation of RNA binding by mutually opposing structured protein domains in this multivalent protein network emerges as a novel mechanism linking associated laterality defects and possibly other ciliopathies to perturbed dynamics in Bicc1 ribonucleoparticle (RNP) formation.