Researchers at the University of Zurich, the Université de Toulouse, and the University of Edinburgh have identified new human adaptor proteins that direct the RNA exosome to specific RNA substrates, according to a study published in Nature Communications.
The RNA exosome-associated helicase MTR4 recruits adaptor proteins containing Arch-Interacting Motifs (AIMs) to selectively degrade RNA targets. Although the exosome acts on diverse RNAs, only a small number of adaptors had previously been identified. The new findings expand the inventory of human adaptors to include a component of the pre-tRNA splicing-ligase complex, a spliceosome-associated factor, and DNTTIP2.
DNTTIP2 is a constituent of the 90S pre-ribosome, which serves as the precursor to the small 40S ribosomal subunit. Structure-guided investigations revealed that the processive exosome core docked by DNTTIP2AIM cooperates with the distributive exonuclease EXOSC10. By binding to distant contact sites on the 90S pre-ribosome, the two enzymes degrade part of the 5′-external transcribed spacer, an RNA scaffold that coordinates early 40S subunit assembly.
The study showed that EXOSC10 is required for productive pre-ribosomal RNA trimming within the 90S pre-ribosome, safeguarding the complex against uncontrolled degradation by the DNTTIP2AIM-docked exosome core. The authors proposed that multivalent contacts provide a structural framework that allows the RNA exosome to coordinate distinct enzymatic activities during ribonucleoprotein particle maturation.
The research, published on August 7, 2026, was dedicated to Cohue Peña, who initiated the project before passing away. Support for the work was provided by the Swiss National Science Foundation, the European Research Council, France's Agence Nationale pour la Recherche, and the University of Zurich.
