Interaction between the RNA-dependent ATPase and poly(A) polymerase subunits of the TRAMP complex is mediated by short peptides and important for snoRNA processing

The RNA exosome is one of the main 3′ to 5′ exoribonucleases in eukaryotic cells. Although it is responsible for degradation or processing of a wide variety of substrate RNAs, it is very specific and distinguishes between substrate and non-substrate RNAs as well as between substrates that need to be 3′ processed and those that need to be completely degraded. This specificity does not appear to be determined by the exosome itself but rather by about a dozen other proteins. Four of these exosome cofactors have enzymatic activity, namely, the nuclear RNA-dependent ATPase Mtr4, its cytoplasmic paralog Ski2 and the nuclear non-canonical poly(A) polymerases, Trf4 and Trf5. Mtr4 and either Trf4 or Trf5 assemble into a TRAMP complex. However, how these enzymes assemble into a TRAMP complex and the functional consequences of TRAMP complex assembly remain unknown. Here, we identify an important interaction site between Mtr4 and Trf5, and show that disrupting the Mtr4/Trf interaction disrupts specific TRAMP and exosome functions, including snoRNA processing.

• Publication year

  2015

• Venue

  Nucleic Acids Research

• Publication date

  2015-01-14

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1093/nar/gkv005PMID 25589546PMCID 4330371
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2014cited by this paper
• A million peptide motifs for the molecular biologist.

  2014cited by this paper
• The molecular architecture of the TRAMP complex reveals the organization and interplay of its two catalytic activities.

  2014influential reference
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  2014cited by this paper
• The exosome‐binding factors Rrp6 and Rrp47 form a composite surface for recruiting the Mtr4 helicase

  2014influential reference
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  2011cited by this paper
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  2011cited by this paper
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  2011cited by this paper
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  2010cited by this paper
• RNA channelling by the eukaryotic exosome

  2010cited by this paper
• Structure and function of the polymerase core of TRAMP, a RNA surveillance complex

  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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  2009cited by this paper
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  2004cited by this paper
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  2002cited by this paper
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  2000cited by this paper
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  2000cited by this paper
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  2000cited by this paper
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  1999cited by this paper
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  1998influential reference
• The 3′ to 5′ degradation of yeast mRNAs is a general mechanism for mRNA turnover that requires the SKI2 DEVH box protein and 3′ to 5′ exonucleases of the exosome complex

  1998influential reference
• The exosome: a conserved eukaryotic RNA processing complex containing multiple 3'-->5' exoribonucleases.

  1997cited by this paper
• Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast.

  1996cited by this paper
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  1996cited by this paper
• The 3' end of yeast 5.8S rRNA is generated by an exonuclease processing mechanism.

  1996cited by this paper
• A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae.

  1989cited by this paper

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  2022cites this paper
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  2020cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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