A bifunctional ARHGEF17-AS1 locus encodes MSEP, a protein that supports mitotic spindle organization
Sagar Mahale1, Vaibhav Chikne2, Nitin Adithya1
1Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.
Abstract:
Bifunctional genomic loci can produce both coding and noncoding outputs, yet the proteins encoded by many such loci remain unexplored. Here, we identify MSEP, a previously uncharacterized ∼54-kDa protein translated from an open reading frame embedded within the antisense RNA locus ARHGEF17-AS1. MSEP localizes to the mitotic spindle and spindle poles, and disruption of its start codon increases spindle abnormalities. MSEP interacts with the spindle-assembly factor TPX2, and its depletion is accompanied by reduced TPX2 abundance. MSEP undergoes cell-cycle-dependent phosphorylation that is regulated by Aurora A and WEE1. Depletion of MSEP is also associated with diminished Aurora A abundance at spindle poles. Genetic uncoupling of MSEP translation from ARHGEF17-AS1 RNA expression supports largely distinct protein- and RNA-mediated pathways that converge on spindle-pole integrity. Together, these results support a bifunctional-locus model in which ARHGEF17-AS1 RNA and its encoded protein, MSEP, contribute to mitotic spindle integrity through distinct, parallel pathways.
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