The C-terminal Region of the Exosome-associated Protein Rrp47 Is Specifically Required for Box C/D Small Nucleolar RNA 3′-Maturation

Costello, Joseph L.; Stead, Jonathan A.; Feigenbutz, Monika; Jones, Rosemary; Mitchell, Phil

doi:10.1074/jbc.m110.162826

Cited by 38 publications

(67 citation statements)

References 54 publications

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“…2B). RNA processing and degradation phenotypes were observed upon induction of GST-Rrp6 NT in the wild-type strain that are similar in nature to those observed in rrp47Δ mutants (Mitchell et al 2003;Costello et al 2011) but considerably weaker, consistent with a mild inhibition of Rrp47 function in wild-type cells upon segregation of Rrp47 from full-length Rrp6 ( Fig. 2B; cf.…”

Section: Rrp47 Is Functional When Physically Segregated From the Catasupporting

confidence: 50%

“…However, Rrp6 lacking the PMC2NT domain shows comparable exonucleolytic activity to the full-length protein on the substrates tested in vitro (Assenholt et al 2008;Wasmuth and Lima 2012). Furthermore, the N-terminal Sas10/C1D domain is able to complement the synthetic lethality of an rrp47Δ rex1Δ mutant but is itself insufficient for the RNA-binding activity of Rrp47 (Costello et al 2011).…”

Section: Introductionmentioning

confidence: 99%

“…This region of Rrp47 has previously been shown to be required for its interaction with the snoRNP proteins Nop56 and Nop58 and for binding to RNA (Costello et al 2011). Genetic assays and Northern analyses show that the resolved Rrp6/Rrp47 complex functions in the processing or degradation of all Rrp6 substrates tested.…”

Section: Introductionmentioning

confidence: 99%

“…As noted above, expression of the N-terminal Sas10/C1D domain of Rrp47 complements the synthetic lethality of rex1Δ rrp47Δ strains (Costello et al 2011). We performed Northern analyses on RNA from a rex1Δ rrp47ΔC strain, which encodes essentially only the Sas10/C1D domain of Rrp47, and from a rex1Δ rrp47 I162X mutant, which encodes a mutant Rrp47 protein lacking a cluster of basic residues at the C terminus of the protein that is required for RNA binding activity in vitro (Costello et al 2011).…”

Section: Rrp47 Is Functional When Physically Segregated From the Catamentioning

confidence: 99%

“…We performed Northern analyses on RNA from a rex1Δ rrp47ΔC strain, which encodes essentially only the Sas10/C1D domain of Rrp47, and from a rex1Δ rrp47 I162X mutant, which encodes a mutant Rrp47 protein lacking a cluster of basic residues at the C terminus of the protein that is required for RNA binding activity in vitro (Costello et al 2011). The rex1Δ rrp47ΔC double mutant, but not the rex1Δ rrp47 I162X double mutant or either rex1Δ or rrp47Δ single mutants, showed a strong accumulation of a heterogeneous population of snR38 molecules with short 3 ′ extensions (Fig.…”

Section: Rrp47 Is Functional When Physically Segregated From the Catamentioning

confidence: 99%

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Rrp47 functions in RNA surveillance and stable RNA processing when divorced from the exoribonuclease and exosome-binding domains of Rrp6

Garland

Feigenbutz

Turner

et al. 2013

RNA

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The eukaryotic exosome exoribonuclease Rrp6 forms a complex with Rrp47 that functions in nuclear RNA quality control mechanisms, the degradation of cryptic unstable transcripts (CUTs), and in the 3 ′ end maturation of stable RNAs. Stable expression of Rrp47 is dependent upon its interaction with the N-terminal domain of Rrp6 (Rrp6 NT ). To address the function of Rrp47 independently of Rrp6, we developed a DECOID (decreased expression of complexes by overexpression of interacting domains) strategy to resolve the Rrp6/Rrp47 complex in vivo and employed mpp6Δ and rex1Δ mutants that are synthetic lethal with loss-of-function rrp47 mutants. Strikingly, Rrp47 was able to function in mpp6Δ and rex1Δ mutants when separated from the catalytic and exosome-binding domains of Rrp6, whereas a truncated Rrp47 protein lacking its C-terminal region caused a block in cell growth. Northern analyses of the conditional mutants revealed a specific block in the 3 ′ maturation of box C/D snoRNAs in the rex1 rrp47 mutant and widespread inhibition of Rrp6-mediated RNA surveillance processes in the mpp6 rrp47 mutant. In contrast, growth analyses and RNA northern blot hybridization analyses showed no effect on the rrp47Δ mutant upon overexpression of the Rrp6 NT domain. These findings demonstrate that Rrp47 and Rrp6 have resolvable functions in Rrp6-mediated RNA surveillance and processing pathways. In addition, this study reveals a redundant requirement for Rrp6 or Rex1 in snoRNA maturation and demonstrates the effective use of the DECOID strategy for the resolution and functional analysis of protein complexes.

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Section: Rrp47 Is Functional When Physically Segregated From the Catasupporting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Rrp47 Is Functional When Physically Segregated From the Catamentioning

confidence: 99%

Section: Rrp47 Is Functional When Physically Segregated From the Catamentioning

confidence: 99%

See 3 more Smart Citations

Rrp47 functions in RNA surveillance and stable RNA processing when divorced from the exoribonuclease and exosome-binding domains of Rrp6

Garland

Feigenbutz

Turner

et al. 2013

RNA

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View full text Add to dashboard Cite

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Comparison of preribosomal RNA processing pathways in yeast, plant and human cells – focus on coordinated action of endo‐ and exoribonucleases

2017

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Edited by Michael IbbaProper regulation of ribosome biosynthesis is mandatory for cellular adaptation, growth and proliferation. Ribosome biogenesis is the most energetically demanding cellular process, which requires tight control. Abnormalities in ribosome production have severe consequences, including developmental defects in plants and genetic diseases (ribosomopathies) in humans. One of the processes occurring during eukaryotic ribosome biogenesis is processing of the ribosomal RNA precursor molecule (pre-rRNA), synthesized by RNA polymerase I, into mature rRNAs. It must not only be accurate but must also be precisely coordinated with other phenomena leading to the synthesis of functional ribosomes: RNA modification, RNA folding, assembly with ribosomal proteins and nucleocytoplasmic RNP export. A multitude of ribosome biogenesis factors ensure that these events take place in a correct temporal order. Among them are endo-and exoribonucleases involved in pre-rRNA processing. Here, we thoroughly present a wide spectrum of ribonucleases participating in rRNA maturation, focusing on their biochemical properties, regulatory mechanisms and substrate specificity. We also discuss cooperation between various ribonucleolytic activities in particular stages of pre-rRNA processing, delineating major similarities and differences between three representative groups of eukaryotes: yeast, plants and humans.Keywords: endoribonuclease; exoribonuclease; pre-rRNA processing; ribosome biogenesis; RNA quality control; RNA trimming Ribosome biosynthesis is a multistep process that includes several tightly controlled events -ribosomal DNA (rDNA) transcription, processing of rRNA precursors into mature molecules, accompanied by binding of ribosome biogenesis factors (RBFs) and ribosomal proteins (RPs), and the final assembly of all Abbreviations CD, catalytic domain; dsRBD, double-stranded RNA-binding domain; ETS, external transcribed spacer; ITS, internal transcribed spacer; LSU, large ribosome subunit (60S); miRNA, microRNA; mRNA, messenger RNA; MRP RNA, noncoding RNA component of the RNase MRP; mTOR, mammalian target of rapamycin; nt(s), nucleotide(s); PIN domain, PilT N-terminal domain; Pol I/II/III, RNA polymerase I/II/III; prerRNA, ribosomal RNA precursor; RBF, ribosome biogenesis factor; RMRP, RNase MRP (mitochondrial RNA processing ribonuclease); RNase, ribonuclease; RNB domain, RNase II domain; RNP, ribonucleoprotein; RP, ribosomal protein; rRNA, ribosomal RNA; siRNA, short interfering RNA; snoRNA, small nucleolar RNA; snoRNP, small nucleolar ribonucleoprotein; snRNA, small nuclear RNA; SSU, small ribosome subunit (40S); TRAMP4 or TRAMP5, Trf4/Air/Mtr4 or Trf5/Air/Mtr4 polyadenylation complex; tRNA, transfer RNA.

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C/D‐box snoRNAs form methylating and non‐methylating ribonucleoprotein complexes: Old dogs show new tricks

et al. 2017

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C/D box snoRNAs (SNORDs) are an abundantly expressed class of short, non-coding RNAs that have been long known to perform 2′-O-methylation of rRNAs. However, approximately half of human SNORDs have no predictable rRNA targets, and numerous SNORDs have been associated with diseases that show no defects in rRNAs, among them Prader-Willi syndrome, Duplication 15q syndrome and cancer. This apparent discrepancy has been addressed by recent studies showing that SNORDs can act to regulate pre-mRNA alternative splicing, mRNA abundance, activate enzymes, and be processed into shorter ncRNAs resembling miRNAs and piRNAs. Furthermore, recent biochemical studies have shown that a given SNORD can form both methylating and non-methylating ribonucleoprotein complexes, providing an indication of the likely physical basis for such diverse new functions. Thus, SNORDs are more structurally and functionally diverse than previously thought, and their role in gene expression is under-appreciated. The action of SNORDs in non-methylating complexes can be substituted with oligonucleotides, allowing devising therapies for diseases like Prader-Willi syndrome.

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The C-terminal Region of the Exosome-associated Protein Rrp47 Is Specifically Required for Box C/D Small Nucleolar RNA 3′-Maturation

Cited by 38 publications

References 54 publications

Rrp47 functions in RNA surveillance and stable RNA processing when divorced from the exoribonuclease and exosome-binding domains of Rrp6

Rrp47 functions in RNA surveillance and stable RNA processing when divorced from the exoribonuclease and exosome-binding domains of Rrp6

Comparison of preribosomal RNA processing pathways in yeast, plant and human cells – focus on coordinated action of endo‐ and exoribonucleases

C/D‐box snoRNAs form methylating and non‐methylating ribonucleoprotein complexes: Old dogs show new tricks

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