Neofunctionalization of ciliary BBS proteins to nuclear roles is likely a frequent innovation across eukaryotes
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Abstract
The eukaryotic BBSome is a transport complex within cilia and assembled by
chaperonin-like BBS proteins. Recent work indicates nuclear functions for BBS
proteins in mammals, but it is unclear how common these are in extant proteins
or when they evolved. We screened for BBS orthologues across a diverse set of
eukaryotes, consolidated nuclear association via signal sequence predictions
and permutation analysis, and validated nuclear localization in mammalian cells
via fractionation and immunocytochemistry. BBS proteins are—with exceptions—
conserved as a set in ciliated species. Predictions highlight five most likely
nuclear proteins and suggest that nuclear roles evolved independently of nuclear
access during mitosis. Nuclear localization was confirmed in human cells. These
findings suggest that nuclear BBS functions are potentially not restricted tomammals,
but may be a common frequently co-opted eukaryotic feature. Understanding
the functional spectrum of BBS proteins will help elucidating their role in gene
regulation, development, and disease.
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iScience, 4, 26, Elsevier, Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis, 2023, https://doi.org/10.1016/j.isci.2023.106410