| Autor: |
Sephora Sallis, Félix-Antoine Bérubé-Simard, Benoit Grondin, Elizabeth Leduc, Fatiha Azouz, Catherine Bélanger, Nicolas Pilon |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Life Science Alliance. 6:e202302133 |
| ISSN: |
2575-1077 |
| DOI: |
10.26508/lsa.202302133 |
| Popis: |
CHARGE syndrome is a neural crest-related disorder mainly caused by mutation of the chromatin remodeler-coding geneCHD7. Alternative causes include mutation of other chromatin and/or splicing factors. One of these additional players is the poorly characterized FAM172A, which we previously found in a complex with CHD7 and the small RNA-binding protein AGO2 at the chromatin–spliceosome interface. Focusing on the FAM172A–AGO2 interplay, we now report that FAM172A is a direct binding partner of AGO2 and, as such, one of the long sought-after regulators of AGO2 nuclear import. We show that this FAM172A function mainly relies on its classical bipartite nuclear localization signal and associated canonical importin-α/β pathway, being enhanced by CK2-induced phosphorylation and abrogated by a CHARGE syndrome-associated missense mutation. Overall, this study thus strengthens the notion that noncanonical nuclear functions of AGO2 and associated regulatory mechanisms might be clinically relevant. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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