Rrp6, Rrp47 and Cofactors of the Nuclear Exosome

Abstract

This chapter reviews the present state of knowledge on the activity of enzymes that function with the RNA exosome in the nucleus. In this compartment, the exosome interacts physically and functionally with the exoribonuclease Rrp6 and several cofactors, most prominently Rrp47 and the TRAMP complex. These interactions decide the fate of RNA precursors from transcription through the formation of mature ribonucleoprotein particles (RNPs) and the export of the RNPs to the cytoplasm. The nuclear exosome catalyzes the formation of the mature 3' ends of many of these RNAs, but in other cases degrades the RNAs to mononucleotides. Co-factors such as Mpp6, TRAMP and the Nrd1/Nab3 complex play important roles in determining the outcome of the interaction of RNPs with the nuclear exosome. The details that govern the specificity of these decisions remain a rich source for future investigation.4

Structural insights into the interaction of the nuclear exosome helicase Mtr4 with the preribosomal protein Nop53

“…In the cytoplasm, the exosome participates in mRNA turnover and in surveillance pathways activated when ribosomes stall on aberrant mRNAs (Schaeffer et al 2011;Graille and Séraphin 2012;Shoemaker and Green 2012). In the nucleus, exosome-mediated degradation also eliminates unnecessary and defective RNAs (such as tRNAs or transcripts generated from pervasive transcription) and is involved in the biogenesis of structured RNAs [such as rRNAs and sn(o)RNAs] (Butler and Mitchell 2011;Sloan et al 2012;Kilchert et al 2016). The processing of rRNA is indeed a major function of this complex, which acts both at early nucleolar stages and at late nucleoplasmic stages of rRNA biogenesis (Thomson et al 2013;Henras et al 2015;Turowski and Tollervey 2015).…”

CryoEM structure of yeast cytoplasmic exosome complex

“…In the best studied Saccharomyces cerevisiae system, Rrp6, an RNase D-type enzyme with distributive exonuclease activity, interacts physically and functionally with the exosome in the nucleus [18]. Rrp6 has been revealed to interact with the Exo10 complex at the top region, next to the entry site of the core [14,15,19].…”

RNA degradation paths in a 12-subunit nuclear exosome complex

“…Biochemical experiments have also suggested the presence of a direct route to Rrp44 that spans 11-12 nucleotides and bypasses the central channel 14 . This core-independent substrate path appears to be used by a subset of nuclear RNAs 16,18 . In the nucleus, the exosome functions with a set of evolutionarily conserved cofactors: the 39-59 distributive exoribonuclease Rrp6 and its obligate interacting partner Rrp47, the essential RNA helicase Mtr4 and the small protein Mpp6 19 . S. cerevisiae Rrp6-Rrp47, Mtr4 and Mpp6 assemble in vitro with Exo-10 to form a 14-subunit complex 20 .…”