RT Journal Article
SR Electronic
T1 The CHARGE syndrome-associated protein FAM172A controls AGO2 nuclear import
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202302133
DO 10.26508/lsa.202302133
VO 6
IS 8
A1 Sephora Sallis
A1 Félix-Antoine Bérubé-Simard
A1 Benoit Grondin
A1 Elizabeth Leduc
A1 Fatiha Azouz
A1 Catherine Bélanger
A1 Nicolas Pilon
YR 2023
UL https://www.life-science-alliance.org/content/6/8/e202302133.abstract
AB 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.