CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cells

Hosoda, Naoe; Kim, Yoon Ki; Lejeune, Fabrice; Maquat, Lynne E.

doi:10.1038/nsmb995

Cited by 134 publications

(162 citation statements)

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“…Our study demonstrated a conserved role of the CBP20/80 nuclear cap binding complex and the 3' to 5' exosome complex in NMD in C. elegans and in mammalian cells (Hosoda et al, 2005;Houseley et al, 2006). CBP80 augments the efficiency of NMD by interacting with UPF1 and promoting the interaction of UPF1 and UPF2.…”

Section: Regulation Of Nmd By Various Biological Processesmentioning

confidence: 62%

“…Among the 83 genes that regulate the expression of gfp:: bro-1(PTC), we identified C. elegans genes whose yeast or mammalian homologs have been implicated in NMD, including eIF-1/T27F7.3, nuclear cap binding protein CBP80/ncbp-1, the exosome complex and NMD3/T25G3.3 (He and Jacobson, 1995;Cui et al, 1999;Hosoda et al, 2005;Houseley et al, 2006). Consistent with previous studies, inactivation of components of EJC did not affect the expression of gfp::bro-1(PTC).…”

Section: © Higher Education Press and Springer-verlag Berlin Heidelbementioning

confidence: 99%

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A genome-wide RNAi screen identifies genes regulating the formation of P bodies in C. elegans and their functions in NMD and RNAi

et al. 2011

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Cytoplasmic processing bodies, termed P bodies, are involved in diverse post-transcriptional processes including mRNA decay, nonsense-mediated RNA decay (NMD), RNAi, miRNA-mediated translational repression and storage of translationally silenced mRNAs. Regulation of the formation of P bodies in the context of multicellular organisms is poorly understood. Here we describe a systematic RNAi screen in C. elegans that identified 224 genes with diverse cellular functions whose inactivations result in a dramatic increase in the number of P bodies. 83 of these genes form a complex functional interaction network regulating NMD. We demonstrate that NMD interfaces with many cellular processes including translation, ubiquitin-mediated protein degradation, intracellular trafficking and cytoskeleton structure. We also uncover an extensive link between translation and RNAi, with different steps in protein synthesis appearing to have distinct effects on RNAi efficiency. Moreover, the intracellular vesicular trafficking network plays an important role in the regulation of RNAi. A subset of genes enhancing P body formation also regulate the formation of stress granules in C. elegans. Our study offers insights into the cellular mechanisms that regulate the formation of P bodies and also provides a framework for system-level understanding of NMD and RNAi in the context of the development of multicellular organisms.

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Section: Regulation Of Nmd By Various Biological Processesmentioning

confidence: 62%

Section: © Higher Education Press and Springer-verlag Berlin Heidelbementioning

confidence: 99%

A genome-wide RNAi screen identifies genes regulating the formation of P bodies in C. elegans and their functions in NMD and RNAi

et al. 2011

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“…NMD in mammalian cells has been proposed to take place during the so-called pioneer round of translation, while transcripts are still bound by the nuclear CBP80/20 complex rather than by eIF4E (Ishigaki et al 2001;Lejeune et al 2002). It was also suggested that CBC might have a role in promoting the interaction of NMD factors with PTC-containing transcripts (Hosoda et al 2005). While our data do not argue against the requirement of CBC for NMD activation, we demonstrate that NMD can be elicited under conditions in which translation is independent of CBC-mediated ribosomal recruitment.…”

Section: Discussionmentioning

confidence: 99%

Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay

Silva

Ribeiro²,

Inácio³

et al. 2008

RNA

140

152

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mRNA surveillance pathways selectively clear defective mRNAs from the cell. As such, these pathways serve as important modifiers of genetic disorders. Nonsense-mediated decay (NMD), the most intensively studied surveillance pathway, recognizes mRNAs with premature termination codons (PTCs). In mammalian systems the location of a PTC more than 50 nucleotides 59 to the terminal exon-exon junction is a critical determinant of NMD. However, mRNAs with nonsense codons that fulfill this requirement but are located very early in the open reading frame can effectively evade NMD. The unexpected resistance of such mRNAs with AUG-proximal PTCs to accelerated decay suggests that important determinants of NMD remain to be identified. Here, we report that an NMD-sensitive mRNA can be stabilized by artificially tethering the cytoplasmic poly(A) binding protein 1, PABPC1, at a PTC-proximal position. Remarkably, the data further suggest that NMD of an mRNA with an AUG-proximal PTC can also be repressed by PABPC1, which might be brought into proximity with the PTC during cap-dependent translation and 43S scanning. These results reveal a novel parameter of NMD in mammalian cells that can account for the stability of mRNAs with AUG-proximal PTCs. These findings serve to expand current mechanistic models of NMD and mRNA translation.

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“…24 The m7G-cap has earlier been shown to be critical for pre-mRNA splicing, shuttling, nonsense-mediated decay, and protein translation. 25,26 Whether defects in mRNA biogenesis play any role in mediating the pleiotrophic phenotype of Bclaf1-deficient mice requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Essential role for Bclaf1 in lung development and immune system function

et al. 2008

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Bcl-2 associated factor 1 (Bclaf1) is a nuclear protein that was originally identified in a screen of proteins that interact with the adenoviral bcl-2 homolog E1B19K. Overexpression of Bclaf1 was shown to result in apoptosis and transcriptional repression that was reversible in the presence of Bcl-2 or Bcl-x L . Furthermore, antiapoptotic members, but not proapoptotic members of the Bcl-2 protein family, were shown to interact with Bclaf1 and prevent its localization to the nucleus. Bclaf1 has also recently been identified as a binding partner for Emerin, a nuclear membrane protein that is mutated in X-linked recessive Emery-Dreifuss muscular dystrophy. To ascertain the in vivo function of Bclaf1, we have generated mice that carry a targeted mutation of the bclaf1 locus. In this study, we show that Bclaf1 is required for proper spatial and temporal organization of smooth muscle lineage during the saccular stage of lung development. We also show that Bclaf1 is dispensable for thymocyte development but is essential for peripheral T-cell homeostasis. Despite its postulated role as a proapoptotic protein, Bclaf1-deficient cells did not show any defect in cell death linked to development or after exposure to various apoptotic stimuli. Our findings show a critical role for Bclaf1 in developmental processes independent of apoptosis. Cell Death and Differentiation (2009) Apoptosis is a critical component of normal development and the cellular response to radio-and chemotherapy. 1,2 Two distinct apoptotic pathways have been characterized: the extrinsic pathway triggered by transmembrane death receptors and the intrinsic pathway that signals through mitochondria. Members of the Bcl-2 protein family primarily impact the intrinsic pathway by controlling mitochondrial membrane permeability, the release of proapoptotic mitochondrial proteins, and caspase activation. 1 Proapoptotic Bcl-2 proteins such as Bak and Bax are activated directly after interactions with the 'BH3-only' Bcl-2 protein Bid. In addition, binding of other BH3-only proteins such as Noxa, Puma, Bad, and Bim to antiapoptotic Bcl-2 proteins (Bcl-2 or Bcl-x L ) results in activation of Bax and Bak. [3][4][5] Bcl-2 associated factor 1 (Bclaf1; also known as Bcl-2-associated transcription factor or Btf) was originally identified in a screen for adenoviral E1B19K protein partners. 6 Subsequent studies with Bclaf1 S , an alternatively-spliced form missing amino acid residues 797-846, showed interactions with Bcl-2 and Bcl-x L . E1B19K, Bcl-2, and Bcl-x L were found to sequester Bclaf1 S to the nuclear periphery and cytoplasm. Ectopic Bclaf1 induced apoptosis as well as transcriptional repression, properties that were reversed in the presence of antiapoptotic Bcl-2 members. 6 Although these findings implicate Bclaf1 in apoptotic signaling, Bclaf1 does not show structural similarities to Bcl-2 family members. Bclaf1 contains an N-terminal tract of Arg-Ser repeats (RS domain) that is typical of pre-mRNA processing factors and was identified in interchromatin granule c...

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CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cells

Cited by 134 publications

References 38 publications

A genome-wide RNAi screen identifies genes regulating the formation of P bodies in C. elegans and their functions in NMD and RNAi

A genome-wide RNAi screen identifies genes regulating the formation of P bodies in C. elegans and their functions in NMD and RNAi

Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay

Essential role for Bclaf1 in lung development and immune system function

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