The Nuclear RNA Exosome and Its Cofactors.

Abstract

The RNA exosome is a highly conserved ribonuclease endowed with 3'-5' exonuclease and endonuclease activities. The multisubunit complex resides in both the nucleus and the cytoplasm, with varying compositions and activities between the two compartments. While the cytoplasmic exosome functions mostly in mRNA quality control pathways, the nuclear RNA exosome partakes in the 3'-end processing and complete decay of a wide variety of substrates, including virtually all types of noncoding (nc) RNAs. To handle these diverse tasks, the nuclear exosome engages with dedicated cofactors, some of which serve as activators by stimulating decay through oligoA addition and/or RNA helicase activities or, as adaptors, by recruiting RNA substrates through their RNA-binding capacities. Most nuclear exosome cofactors contain the essential RNA helicase Mtr4 (MTR4 in humans). However, apart from Mtr4, nuclear exosome cofactors have undergone significant evolutionary divergence. Here, we summarize biochemical and functional knowledge about the nuclear exosome and exemplify its cofactor variety by discussing the best understood model organisms-the budding yeast Saccharomyces cerevisiae, the fission yeast Schizosaccharomyces pombe, and human cells.