RNA Degradation by the Exosome Is Promoted by a Nuclear Polyadenylation Complex

LaCava, John; Houseley, Jonathan; Saveanu, Cosmin; Petfalski, Elisabeth; Thompson, Elizabeth L.; Jacquier, Alain; Tollervey, David

doi:10.1016/j.cell.2005.04.029

Cited by 810 publications

(1,016 citation statements)

References 42 publications

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“…Both the Nrd1/Nab3/Sen1 complex, which binds CUTs in a sequence dependent manner, 14 and modification of CUTs by addition of a short polyA tract by the Trf-Air-Mtr4 polyadenylation (TRAMP) complex activate exosome-mediated degradation. 15,16 This exosome-dependent degradation explains why the CUTs are rarely seen in genomic assays.…”

Section: Divergent Transcription In Mammalsmentioning

confidence: 99%

Divergent transcription: A new feature of active promoters

Seila¹,

Core²,

Lis³

et al. 2009

Cell Cycle

169

164

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Section: Divergent Transcription In Mammalsmentioning

confidence: 99%

Divergent transcription: A new feature of active promoters

Seila¹,

Core²,

Lis³

et al. 2009

Cell Cycle

169

164

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“…(41/42-like heterodimer) [31] Cofactors for the exosomes without 3¢ exoRNase activity RhlB RNA helicase [50] Degradosome complex in certain bacteria [51] Ski7p and Ski RNA helicase complex [52,53] Mtr4p RNA helicase and TRAMP complex [54], Rrp47 [48], Nrd1 [55] RNA helicase associated with AU-rich element or RHAU [56], KSRP [57], TTP [58] a It is not known yet whether human nuclear and cytoplasmic exosomes contain different components.…”

Section: Chloroplastmentioning

confidence: 99%

“…Unlike the RNase E-RhlB interaction, the interaction between PNPase a-and b-subunits is rather unstable, which most likely ensures a transient association between the protein and the ring-shaped machine core, as with accessory proteins of the eukaryotic exosome [40]. The RNA degradation function of yeast nuclear exosome is promoted by a nuclear polyadenylation complex termed the TRAMP complex [54]. The TRAMP complex consists of a poly(A) polymerase (Trf4p and/or Trf5p), a zinc knuckle protein (Air2p) and a RNA-helicase (Mtr4p).…”

Section: Chloroplastmentioning

confidence: 99%

The PNPase, exosome and RNA helicases as the building components of evolutionarily-conserved RNA degradation machines

2007

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The structure and function of polynucleotide phosphorylase (PNPase) and the exosome, as well as their associated RNA-helicases proteins, are described in the light of recent studies. The picture raised is of an evolutionarily conserved RNA-degradation machine which exonucleolytically degrades RNA from 3¢ to 5¢. In prokaryotes and in eukaryotic organelles, a trimeric complex of PNPase forms a circular doughnutshaped structure, in which the phosphorolysis catalytic sites are buried inside the barrel-shaped complex, while the RNA binding domains create a pore where RNA enters, reminiscent of the protein degrading complex, the proteasome. In some archaea and in the eukaryotes, several different proteins form a similar circle-shaped complex, the exosome, that is responsible for 3¢ to 5¢ exonucleolytic degradation of RNA as part of the processing, quality control, and general RNA degradation process. Both PNPase in prokaryotes and the exosome in eukaryotes are found in association with protein complexes that notably include RNA helicase.

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“…The nucleic acid-binding protein Rrp47 is necessary for the processing of rRNA, snoRNA, and snRNA precursors (Mitchell et al, 2003). The TRAMP polyadenylation complex, furthermore, acts as a cofactor for the degradation of cryptic transcripts and structured RNA substrates (LaCava et al, 2005;Vanacova et al, 2005), and for mRNA surveillance (Rougemaille et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

The Exosome Associates Cotranscriptionally with the Nascent Pre-mRNP through Interactions with Heterogeneous Nuclear Ribonucleoproteins

Hessle¹,

Björk²,

Sokolowski³

et al. 2009

MBoC

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Eukaryotic cells have evolved quality control mechanisms to degrade aberrant mRNA molecules and prevent the synthesis of defective proteins that could be deleterious for the cell. The exosome, a protein complex with ribonuclease activity, is a key player in quality control. An early quality checkpoint takes place cotranscriptionally but little is known about the molecular mechanisms by which the exosome is recruited to the transcribed genes. Here we study the core exosome subunit Rrp4 in two insect model systems, Chironomus and Drosophila. We show that a significant fraction of Rrp4 is associated with the nascent pre-mRNPs and that a specific mRNA-binding protein, Hrp59/hnRNP M, interacts in vivo with multiple exosome subunits. Depletion of Hrp59 by RNA interference reduces the levels of Rrp4 at transcription sites, which suggests that Hrp59 is needed for the exosome to stably interact with nascent pre-mRNPs. Our results lead to a revised mechanistic model for cotranscriptional quality control in which the exosome is constantly recruited to newly synthesized RNAs through direct interactions with specific hnRNP proteins. INTRODUCTIONExpression of protein-coding genes is a complex multistep process. Precursor messenger RNAs (pre-mRNAs) are synthesized by RNA polymerase II (Pol-II) and assembled into ribonucleoprotein (RNP) complexes during transcription. The pre-mRNPs must be processed to become mature mRNPs, which are exported to the cytoplasm and translated into protein. Mutations in the DNA or errors in the transcription and processing reactions can lead to the synthesis of aberrant mRNPs. Eukaryotic cells have evolved quality control mechanisms that identify aberrant mRNPs and prevent their expression into protein. In the yeast Saccharomyces cerevisiae there are at least three nuclear steps of mRNP biogenesis that are under surveillance: the cleavage and polyadenylation of the 3Ј end (Hilleren et al., 2001), the assembly of the mRNA-protein complexes (Zenklusen et al., 2002;Luna et al., 2005), and the removal of introns (Galy et al., 2004). In all cases, mRNPs with assembly and/or processing defects are detected by nuclear surveillance mechanisms, retained in the nucleus, and degraded (reviewed by Vinciguerra and Stutz, 2004;Sommer and Nehrbass, 2005;Saguez et al., 2005). Genetic studies in S. cerevisiae have identified the nuclear exosome as a key player in the recognition and retention of defective transcripts (reviewed by Jensen et al., 2003;Houseley et al., 2006;Vanacova and Stefl, 2007;Schmid and Jensen, 2008).The exosome is a protein complex with ribonuclease activity (Mitchell et al., 1997;Allmang et al., 1999;Mitchell and Tollervey, 2000). The core of the exosome has a barrel-like architecture (reviewed by Lorentzen et al., 2008). The barrel is made of nine protein subunits organized into two rings, a hexameric ring and a trimeric ring, and the structure of the barrel is conserved throughout evolution (Lorentzen et al., 2005;Liu et al., 2006;Wang et al., 2007). Two additional proteins, Dis3/Rrp44 and R...

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RNA Degradation by the Exosome Is Promoted by a Nuclear Polyadenylation Complex

Cited by 810 publications

References 42 publications

Divergent transcription: A new feature of active promoters

Divergent transcription: A new feature of active promoters

The PNPase, exosome and RNA helicases as the building components of evolutionarily-conserved RNA degradation machines

The Exosome Associates Cotranscriptionally with the Nascent Pre-mRNP through Interactions with Heterogeneous Nuclear Ribonucleoproteins

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