The rixosome is a large protein complex found in mammalian cells that is essential for both ribosome production and the maintenance of tightly packed regions of DNA called heterochromatin. At its core are three structural proteins that act as a scaffold for several enzyme-containing modules, including an RNA-processing unit known as RNase PNK.
Using cryo-electron microscopy, Jacob Gordon, a PhD student jointly supervised by the Warren and Stanley (NIH, North Carolina) labs, determined detailed structures of human RNase PNK bound to RNA and ATP-like molecules. These structures revealed the overall shape of the complex, which resembles a butterfly, and showed how RNA is positioned and chemically modified within the enzyme. In particular, the study explains how the polynucleotide kinase NOL9 adds a phosphate group to the 5′ end of RNA, an important step in RNA processing.
Jacob also uncovered how RNase PNK is incorporated into the larger rixosome through a specific region of the LAS1L protein. In addition, he found that the RNA-degrading enzyme XRN2 directly interacts with RNase PNK and preferentially degrades RNA molecules that have been phosphorylated by NOL9. This finding links RNA processing by the rixosome to subsequent RNA degradation.
Together, the results provide a more complete picture of how the rixosome coordinates multiple enzymatic activities to process ITS2, a crucial segment of precursor ribosomal RNA, during ribosome assembly. The work advances our understanding of the molecular mechanisms that ensure efficient ribosome production in human cells.