| First Author | Sallis S | Year | 2023 |
| Journal | Life Sci Alliance | Volume | 6 |
| Issue | 8 | PubMed ID | 37221016 |
| Mgi Jnum | J:349229 | Mgi Id | MGI:7485167 |
| Doi | 10.26508/lsa.202302133 | Citation | Sallis S, et al. (2023) The CHARGE syndrome-associated protein FAM172A controls AGO2 nuclear import. Life Sci Alliance 6(8) |
| abstractText | 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-alpha/beta 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. |
