title: Genetic interactions suggest multiple distinct roles of the arch and core helicase domains of Mtr4 in Rrp6 and exosome function.
abstract: The RNA exosome is responsible for a wide variety of RNA processing and degradation reactions. The activity and specificity of the RNA exosome is thought to be controlled by a number of cofactors. Mtr4 is an essential RNA-dependent adenosine triphosphatase that is required for all of the nuclear functions of the RNA exosome. The crystal structure of Mtr4 uncovered a domain that is conserved in the RNA exosome cofactors Mtr4 and Ski2 but not in other helicases, suggesting it has an important role related to exosome activation. Rrp6 provides the nuclear exosome with one of its three nuclease activities, and previous findings suggested that the arch domain is specifically required for Rrp6 functions. Here, we report that the genetic interactions between the arch domain of Mtr4 and Rrp6 cannot be explained by the arch domain solely acting in Rrp6-dependent processing reactions. Specifically, we show that the arch domain is not required for all Rrp6 functions, and that the arch domain also functions independently of Rrp6. Finally, we show that the arch domain of Ski2, the cytoplasmic counterpart of Mtr4, is required for Ski2's function, thereby confirming that the arch domains of these cofactors function independently of Rrp6.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Texas Health Science Center-Houston and The University of Texas Graduate School of Biomedical Sciences, 6431 Fannin Street, MSB 1.212, Houston, TX 77030, USA.
authors.forename: A Alejandra
authors.initials: AA
authors.lastname: Klauer
authors.forename: Ambro
authors.initials: A
authors.lastname: van Hoof
mesh_terms: D003593:Cytoplasm / Q000201:enzymology; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D063326:Exosome Multienzyme Ribonuclease Complex / Q000235:genetics*; D017353:Gene Deletion; D017434:Protein Structure, Tertiary / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional; D020537:RNA, Small Nucleolar / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D020537:RNA, Small Nucleolar; C081929:SKI2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012321:DNA-Directed RNA Polymerases; C506067:Trf5 protein, S cerevisiae; D063326:Exosome Multienzyme Ribonuclease Complex; C112610:RRP6 protein, S cerevisiae; C101004:MTR4 protein, S cerevisiae; D053487:DEAD-box RNA Helicases