2023-09-25 スイス連邦工科大学ローザンヌ校(EPFL)
◆また、胚の発生中に内部器官の正しい非対称な配置を妨げることもあります。このような非対称性の例として、通常は左側に位置する心臓があり、その血管を左右非対称に正しく配置することは、体内の酸素供給にとって重要です。
◆新しい研究では、繊毛による流体感知が器官の非対称性を指定するために活性化される要因が、これまで謎だった2つの他の繊毛症関連タンパク質によって密接に調節されていることが明らかにされました。この研究は、遺伝子疾患治療などの新たな研究分野を開く可能性があります。
<関連情報>
- https://actu.epfl.ch/news/the-dance-of-organ-positioning-a-tango-of-three-pr/
- https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002302
Bicc1リボ核タンパク質複合体は、ANKS6が誘導するANKS3の構造リモデリングによって臓器の左右性を決定する Bicc1 ribonucleoprotein complexes specifying organ laterality are licensed by ANKS6-induced structural remodeling of associated ANKS3
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
PLoS Biology Published: September 21, 2023
DOI:https://doi.org/10.1371/journal.pbio.3002302
Abstract
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.
