SKI complex: A multifaceted cytoplasmic RNA exosome cofactor in mRNA metabolism with links to disease, developmental processes, and antiviral responses

Abstract

AbstractRNA stability and quality control are integral parts of gene expression regulation. A key factor shaping eukaryotic transcriptomes, mainly via 3′–5′ exoribonucleolytic trimming or degradation of diverse transcripts in nuclear and cytoplasmic compartments, is the RNA exosome. Precise exosome targeting to various RNA molecules requires strict collaboration with specialized auxiliary factors, which facilitate interactions with its substrates. The predominant class of cytoplasmic RNA targeted by the exosome are protein‐coding transcripts, which are carefully scrutinized for errors during translation. Normal, functional mRNAs are turned over following protein synthesis by the exosome or by Xrn1 5′–3′‐exonuclease, acting in concert with Dcp1/2 decapping complex. In turn, aberrant transcripts are eliminated by dedicated surveillance pathways, triggered whenever ribosome translocation is impaired. Cytoplasmic 3′–5′ mRNA decay and surveillance are dependent on the tight cooperation between the exosome and its evolutionary conserved co‐factor—the SKI (superkiller) complex (SKIc). Here, we summarize recent findings from structural, biochemical, and functional studies of SKIc roles in controlling cytoplasmic RNA metabolism, including links to various cellular processes. Mechanism of SKIc action is illuminated by presentation of its spatial structure and details of its interactions with exosome and ribosome. Furthermore, contribution of SKIc and exosome to various mRNA decay pathways, usually converging on recycling of ribosomal subunits, is delineated. A crucial physiological role of SKIc is emphasized by describing association between its dysfunction and devastating human disease—a trichohepatoenteric syndrome (THES). Eventually, we discuss SKIc functions in the regulation of antiviral defense systems, cell signaling and developmental transitions, emerging from interdisciplinary investigations.This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Turnover and Surveillance > Regulation of RNA Stability RNA Interactions with Proteins and Other Molecules > RNA‐Protein Complexes