Interaction Profiling Identifies the Human Nuclear Exosome Targeting Complex

Lubas, Michał; Christensen, Marianne S.; Kristiansen, Maiken Søndergaard; Domanski, Michal; Falkenby, Lasse Gaarde; Lykke‐Andersen, Søren; Andersen, Jens S.; Dziembowski, Andrzej; Jensen, Torben Heick

doi:10.1016/j.molcel.2011.06.028

Cited by 361 publications

(598 citation statements)

References 56 publications

Supporting

Mentioning

557

Contrasting

Order By: Relevance

“…The NNS complex (Nrd1p, Nab3p, and Sen1p) requires Exo11 to process some snRNAs and snoRNAs, which are transcribed by RNP II (Kim et al, 2006). Additionally, in human cells, Exo11 associates with the NEXT complex (nuclear exosome targeting complex), which consists of hMTR4, zinc knuckle protein ZCCHC8, and RNA binding protein RBM7, to facilitate the degradation of transcripts upstream of promoters (Lubas et al, 2011).…”

Section: Exosomementioning

confidence: 99%

mRNA stability in the nucleus

Liu

Luo

Wen

2014

J. Zhejiang Univ. Sci. B

View full text Add to dashboard Cite

Abstract:Eukaryotic gene expression is controlled by different levels of biological events, such as transcription factors regulating the timing and strength of transcripts production, alteration of transcription rate by RNA processing, and mRNA stability during RNA processing and translation. RNAs, especially mRNAs, are relatively vulnerable molecules in living cells for ribonucleases (RNases). The maintenance of quality and quantity of transcripts is a key issue for many biological processes. Extensive studies draw the conclusion that the stability of RNAs is dedicated-regulated, occurring co-and post-transcriptionally, and translation-coupled as well, either in the nucleus or cytoplasm. Recently, RNA stability in the nucleus has aroused much research interest, especially the stability of newly-made transcripts. In this article, we summarize recent progresses on mRNA stability in the nucleus, especially focusing on quality control of newly-made RNA by RNA polymerase II in eukaryotes.

show abstract

Section: Exosomementioning

confidence: 99%

mRNA stability in the nucleus

Liu

Luo

Wen

2014

J. Zhejiang Univ. Sci. B

View full text Add to dashboard Cite

show abstract

“…How mRNAs are recognized as incorrect is still unclear, however, the nuclear pore complex (NPC) proteins Mlp1, Mlp2, Nup60 and Pml39 as well as the nuclear envelope protein Esc1 and the pre-mRNA retention and splicing complex protein Pml1 may play a role as their absence or mutations in their genes lead to the leakage of unspliced mRNAs into the cytoplasm 2,5 . Another exosome adapter was identified in mammalian cells and termed the nuclear exosome targeting (NEXT) complex, which is required for the degradation of noncoding transcripts 13 . It contains MTR4, an RNA-binding motif containing protein, RBM7 and the zinc finger CCHC domaincontaining protein 8 (ZCCHC8).…”

mentioning

confidence: 99%

“…It contains MTR4, an RNA-binding motif containing protein, RBM7 and the zinc finger CCHC domaincontaining protein 8 (ZCCHC8). Both, RBM7 and ZCCHHC8 co-purify with members of the serine/arginine (SR) protein family 13,14 . These findings link the SR proteins, which are known for their function in splicing, with the exosome and its co-factors, important for RNA degradation and it was suggested that the SR proteins might assist the NEXT complex in higher eukaryotes 3 .…”

mentioning

confidence: 99%

Quality control of spliced mRNAs requires the shuttling SR proteins Gbp2 and Hrb1

et al. 2014

View full text Add to dashboard Cite

Eukaryotic cells have to prevent the export of unspliced pre-mRNAs until intron removal is completed to avoid the expression of aberrant and potentially harmful proteins. Only mature mRNAs associate with the export receptor Mex67/TAP and enter the cytoplasm. Here we show that the two shuttling serine/arginine (SR)-proteins Gbp2 and Hrb1 are key surveillance factors for the selective export of spliced mRNAs in yeast. Their absence leads to the significant leakage of unspliced pre-mRNAs into the cytoplasm. They bind to pre-mRNAs and the spliceosome during splicing, where they are necessary for the surveillance of splicing and the stable binding of the TRAMP complex to spliceosome-bound transcripts. Faulty transcripts are marked for their degradation at the nuclear exosome. On correct mRNAs the SR proteins recruit Mex67 upon completion of splicing to allow a quality controlled nuclear export. Altogether, these data identify a role for shuttling SR proteins in mRNA surveillance and nuclear mRNA quality control.

show abstract

“…The TRAMP complex consists of three subunits that are highly conserved in eukaryotes: a noncanonical poly(A) polymerase (Trf4p or Trf5p in Saccharomyces cerevisiae), a Zn-knuckle protein (Air2p or Air1p), and the RNA helicase Mtr4p (4)(5)(6)(7). TRAMP assists RNA degradation by the nuclear exosome, most notably by appending short (∼4-5 nt) oligo(A) tails at the 3′ ends of RNAs slated for exosome-mediated degradation (4,5,(8)(9)(10).…”

mentioning

confidence: 99%

RNA unwinding by the Trf4/Air2/Mtr4 polyadenylation (TRAMP) complex

Jia

Wang

Anderson

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Many RNA-processing events in the cell nucleus involve the Trf4/ Air2/Mtr4 polyadenylation (TRAMP) complex, which contains the poly(A) polymerase Trf4p, the Zn-knuckle protein Air2p, and the RNA helicase Mtr4p. TRAMP polyadenylates RNAs designated for processing by the nuclear exosome. In addition, TRAMP functions as an exosome cofactor during RNA degradation, and it has been speculated that this role involves disruption of RNA secondary structure. However, it is unknown whether TRAMP displays RNA unwinding activity. It is also not clear how unwinding would be coordinated with polyadenylation and the function of the RNA helicase Mtr4p in modulating poly(A) addition. Here, we show that TRAMP robustly unwinds RNA duplexes. The unwinding activity of Mtr4p is significantly stimulated by Trf4p/Air2p, but the stimulation of Mtr4p does not depend on ongoing polyadenylation. Nonetheless, polyadenylation enables TRAMP to unwind RNA substrates that it otherwise cannot separate. Moreover, TRAMP displays optimal unwinding activity on substrates with a minimal Mtr4p binding site comprised of adenylates. Our results suggest a model for coordination between unwinding and polyadenylation activities by TRAMP that reveals remarkable synergy between helicase and poly(A) polymerase.he Trf4/Air2/Mtr4 polyadenylation (TRAMP) complex is involved in nuclear RNA surveillance, 3′-end processing of rRNA, small nucleolar RNAs (snoRNAs), and snRNAs, and in gene silencing and chromatin maintenance (1-3). The TRAMP complex consists of three subunits that are highly conserved in eukaryotes: a noncanonical poly(A) polymerase (Trf4p or Trf5p in Saccharomyces cerevisiae), a Zn-knuckle protein (Air2p or Air1p), and the RNA helicase Mtr4p (4-7). TRAMP assists RNA degradation by the nuclear exosome, most notably by appending short (∼4-5 nt) oligo(A) tails at the 3′ ends of RNAs slated for exosome-mediated degradation (4,5,(8)(9)(10). In addition, it has been speculated that TRAMP enables the nuclear exosome to efficiently degrade structured RNA through unwinding activity associated with Mtr4p (1, 2, 11-13).However, RNA helicase activity has not been demonstrated for TRAMP. Though Mtr4p alone has been shown to unwind RNA duplexes in vitro (12, 13), it is not known whether binding of Trf4p/Air2p abolishes, decreases, increases, or otherwise alters this helicase activity. This question is important for TRAMP function, because Mtr4p and Trf4p operate with opposite polarities. Mtr4p only unwinds duplexes with a 3′ unpaired region, i.e., with a 3′ to 5′ polarity (12, 13). Trf4p polyadenylates the 3′ end of RNA and thus possesses 5′ to 3′ polarity (4, 5). How unwinding and polyadenylation with opposite polarities are coordinated in one complex is not readily apparent.Moreover, Mtr4p controls the lengths of poly(A) tails appended by TRAMP (9). This role of Mtr4p requires ATP, but does not involve unwinding (9). Instead, Mtr4p binds to the 3′ end of the RNA, detects the number of 3′-terminal adenosines, and, in response, modulates ATP affinity and adenylatio...

show abstract

Interaction Profiling Identifies the Human Nuclear Exosome Targeting Complex

Cited by 361 publications

References 56 publications

mRNA stability in the nucleus

mRNA stability in the nucleus

Quality control of spliced mRNAs requires the shuttling SR proteins Gbp2 and Hrb1

RNA unwinding by the Trf4/Air2/Mtr4 polyadenylation (TRAMP) complex

Contact Info

Product

Resources

About