A new regulatory pathway of mRNA export by an F‐box protein, Mdm30

Abstract

Regulatory role of ubiquitylation has been implicated in various steps of gene expression and mRNA export is not an exception. Specificity of this modification is conferred by E3 ligases whose function is dictated by specific domains they possess. Role of HECT domain containing E3 ligases like Tom1 and Rsp5 have previously been implicated in regulation of mRNA export. However, pertaining to diversity of E3 ligases, the roles of other ligases in this aspect of gene expression is unknown. Interestingly, our recent work established the role of an F‐box protein, Mdm30, in stimulation of mRNA export. F‐box proteins are bonafide members of RING domain containing SCF (Skp1‐Cullin‐F box) ligase complex. To elucidate the mechanism‐of‐action of Mdm30, we carried out a series of experiments. We find that Mdm30 ubiquitylates the Sub2 component of Transcription/Export complex (TREX) in SCF dependent manner. Ubiquitylated‐Sub2 is subsequently degraded by 26S proteasome complex. Such targeted degradation of Sub2 enhances the recruitment of mRNA export adaptor, Yra1, onto active gene to promote mRNA export. Collectively, these results provide a new regulatory pathway of mRNA export, and will be presented in this conference.Funding: Excellence in Academic Medicine (EAM) from the School of Medicine, Southern Illinois University.