Cover image

The human DDX3X and DDX3Y genes on Chr X and Chr Y, respectively, encode RNA helicases critical for translation and other cellular processes. In this issue, it is shown that DDX3X and DDX3Y are negatively, post-transcriptionally cross-regulated in 46,XY cells, and that DDX3X is negatively, post-transcriptionally auto-regulated in 46,XX cells. This means that perturbations to one allele (of DDX3X or DDX3Y) are buffered by upregulation of the other allele, making this the first instance of an X–Y gene pair with cross-regulatory capabilities. The cover depicts this intricate buffering of DDX3X and DDX3Y dosage as orange and purple rocks balanced on beams (Chr X and Chr Y, respectively). This dynamic system rests on a representation of the ancestral DDX3X ortholog (in gray), the autosomal precursor from which these human X and Y genes evolved. (Cover illustration by Caitlin Rausch, https://www.warblercreative.work/. [For details, see Rengarajan et al., pp. 20–30.])