期刊
LIFE SCIENCE ALLIANCE
卷 6, 期 8, 页码 -出版社
LIFE SCIENCE ALLIANCE LLC
DOI: 10.26508/lsa.202302133
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CHARGE syndrome is primarily caused by CHD7 mutation, a chromatin remodeler-coding gene. FAM172A, a poorly characterized factor, is found to be a binding partner of AGO2 and regulates AGO2 nuclear import. The study highlights the importance of noncanonical nuclear functions of AGO2 and its regulatory mechanisms.
CHARGE syndrome is a neural crest-related disorder mainly caused by mutation of the chromatin remodeler-coding gene CHD7. Alter-native 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 ab-rogated 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.
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