Structure of the nuclear exosome captured on a maturing preribosome

Abstract

The RNA exosome complex processes and degrades a wide range of transcripts, including ribosomal RNAs (rRNAs). We used cryo-electron microscopy to visualize the yeast nuclear exosome holocomplex captured on a precursor large ribosomal subunit (pre-60<i>S</i>) during 7<i>S</i>-to-5.8<i>S</i> rRNA processing. The cofactors of the nuclear exosome are sandwiched between the ribonuclease core complex (Exo-10) and the remodeled "foot" structure of the pre-60<i>S</i> particle, which harbors the 5.8<i>S</i> rRNA precursor. The exosome-associated helicase Mtr4 recognizes the preribosomal substrate by docking to specific sites on the 25<i>S</i> rRNA, captures the 3' extension of the 5.8<i>S</i> rRNA, and channels it toward Exo-10. The structure elucidates how the exosome forms a structural and functional unit together with its massive pre-60<i>S</i> substrate to process rRNA during ribosome maturation.