TY - JOUR T1 - The CHARGE syndrome-associated protein FAM172A controls AGO2 nuclear import JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202302133 VL - 6 IS - 8 SP - e202302133 AU - Sephora Sallis AU - Félix-Antoine Bérubé-Simard AU - Benoit Grondin AU - Elizabeth Leduc AU - Fatiha Azouz AU - Catherine Bélanger AU - Nicolas Pilon Y1 - 2023/08/01 UR - https://www.life-science-alliance.org/content/6/8/e202302133.abstract N2 - CHARGE syndrome is a neural crest-related disorder mainly caused by mutation of the chromatin remodeler-coding gene CHD7. 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. ER -