Structural insights into the RNA degradation mechanism

Abstract

RNA degradation is determinant in the control of gene expression. The maturation, turnover and quality control of RNA is performed by many different classes of ribonucleases. One class of these enzymes degrade single-stranded RNA from its 3’ end and release ribonucleoside 5’-monophosphates [1]. Exoribonucleases can act independently or as a component of the exosome, an essential RNA-degradingmultiprotein complex [2]. X-ray crystallographic structures of both the ligand-free (at 2.4 A resolution) and RNA-bound (at 2.8 A resolution) forms of an exoribonuclease were solved using ESRF synchrotron data byMIRAS using selenomethionine and Hg acetate derivatives. The structure is organized into 4 domains, three cold shock and one catalytic domain that shows an unprecedented αβ-fold. The enzyme establishes contacts with RNA in two distinct regions, the ‘anchor’ and the ‘catalytic’ regions, which act synergistically to provide catalysis. The active site is buried within the catalytic domain, in a pocket formed by four conserved sequence motifs. The structure shows that the catalytic pocket is only accessible to single stranded RNA, and explains the specificity for RNA versus DNA cleavage. It also explains the dynamicmechanism ofRNAdegradation by providing the structural basis for RNA translocation and enzyme processivity [3].