|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online April 28, 2005
doi: 10.1242/10.1242/jcs.01701
Cell Science at a Glance |
Department of Biochemistry and Biophysics, School of Medicine and Dentistry, 601 Elmwood Avenue, Box 712, University of Rochester, Rochester, NY 14642, USA
(e-mail: lynne_maquat{at}urmc.rochester.edu)
Nonsense-mediated mRNA decay (NMD) in mammalian cells generally degrades mRNAs that terminate translation more than 50-55 nucleotides upstream of a splicing-generated exon-exon junction (reviewed in Maquat, 2004a
; Nagy and Maquat, 1998). Notably, dependence on exon-exon junctions distinguishes NMD in mammalian cells from NMD in all other organisms that have been examined, including Saccharomyces cerevisiae and Drosophila melanogaster (reviewed in Maquat, 2004b). NMD downregulates spliced mRNAs that prematurely terminate translation so production of the potentially toxic truncated proteins that they encode. NMD also downregulates naturally occurring mRNAs, such as an estimated one-third of alternatively spliced mRNAs, certain selenoprotein mRNAs, some mRNAs that have upstream open reading frames, and some mRNAs that contain an intron within the 3' untranslated region (Hillman et al., 2004; Mendell et al., 2004; Moriarty et al., 1998). In fact, it is thought that NMD has been maintained throughout evolution not only because it degrades transcripts that are the consequence of routine abnormalities in gene expression but also because it is widely used to achieve proper levels of gene expression. Although disease-associated mutations that result in the premature termination of translation led to the discovery of NMD, it is not likely that this type of mutation ever drove significant evolutionary selection. Nevertheless, some of these mutations nicely illustrate the importance of NMD. For example, nonsense mutations within the last exon of the human ß-globin gene do not elicit NMD because there is no downstream exon-exon junction. As a consequence, the resulting truncated ß-globin has near-normal abundance, fails to properly associate with 
-globin and causes a dominantly inherited form of what is otherwise (e.g. for nonsense codons located within exons other than the last exon) a recessively inherited thalassemia (Thein, 2004).
|
The importance of NMD is exemplified by the findings that mouse embryos that cannot perform NMD because they lack a key NMD protein, Upf1, resorb shortly after implantation (Medghalchi et al., 2001). Furthermore, blastocysts that have the same defect, isolated 3.5 days post-coitum, undergo apoptosis in culture after a brief growth period (Medghalchi et al., 2001). The inviability of NMD-deficient embryos and cells probably reflects the combined failure to regulate natural substrates properly and eliminate transcripts that were generated in error. Note that, Upf1 has been shown to function in other pathways, as well as NMD (see below), which may also contribute to the observed inviability.
NMD in mammalian cells is a consequence of a pioneer round of translation (Chiu et al., 2004; Ishigaki et al., 2001; Lejeune et al., 2004). As illustrated in the poster, precursor (pre)-mRNA in the nucleus is bound to by the major nuclear cap-binding protein (CBP) CBP80-CBP20 heterodimer and, after 3'-end formation, the major nuclear poly(A)-binding protein (PABP) PABPN1 (Chiu et al., 2004; Ishigaki et al., 2001). Pre-mRNA splicing generates spliced mRNA that is bound by CBP80, CBP20, PABPN1 and the major cytoplasmic PABPC (Chiu et al., 2004; Ishigaki et al., 2001; Lejeune et al., 2004) as well as an exon junction complex (EJC) of proteins that is deposited, as a consequence of splicing, 
20-24 nucleotides upstream of each exon-exon junction (Le Hir et al., 2000a; Le Hir et al., 2000b). Constituents of EJCs include Y14, RNPS1, SRm160, REF/Aly, UAP56, Magoh, Pnn/DRS, eIF4AIII, PYM and Barentsz/MLN51 (Bono et al., 2004; Chan et al., 2004; Custodio et al., 2004; Degot et al., 2004; Ferraiuolo et al., 2004; Kataoka et al., 2000; Kim et al., 2001; Le Hir et al., 2001; Le Hir et al., 2000a; Le Hir et al., 2000b; Lejeune et al., 2002; Li et al., 2003; Luo et al., 2001; Palacios et al., 2004; Shibuya et al., 2004). The EJC also contains additional proteins, including the NMD factors Upf3 (also called Upf3a) or Upf3X (also called Upf3b), Upf2 and, presumably transiently, Upf1 (Kim et al., 2004; Lykke-Andersen et al., 2000; Lykke-Andersen et al., 2001; Mendell et al., 2000; Ohnishi et al., 2003; Serin et al., 2001). Either Upf3 or Upf3X, each of which is mostly nuclear but shuttles to the cytoplasm and interacts with Upf2, is thought to recruit Upf2, which concentrates along the cytoplasmic side of the nuclear envelope (Kadlec et al., 2004; Lykke-Andersen et al., 2000; Serin et al., 2001).
The resulting mRNP constitutes the pioneer translation initiation complex (Chiu et al., 2004; Ishigaki et al., 2001; Lejeune et al., 2002; Lejeune et al., 2004). This complex is thought to undergo a `pioneer' round of translation either in association with nuclei, in the case of mRNAs that are subject to nucleus-associated NMD, or in the cytoplasm, in the case of mRNAs that are subject to cytoplasmic NMD. If NMD occurs, it is the consequence of nonsense codon (NC) recognition during this pioneer round of translation (Chiu et al., 2004; Ishigaki et al., 2001; Lejeune et al., 2004). Upf1 may function as a component of the translation termination complex before it functions in NMD, considering that NMD requires translation termination and Upf1 associates with eukaryotic translation release factors 1 (F. Lejeune and L.E.M., unpublished) and 3 (G. Singh and J. Lykke-Andersen, personal communication). Upf1 might associate with mRNA regardless of whether termination occurs at a position that elicits NMD. If translation terminates at an NC that resides more than 50-55 nucleotides upstream of an exon-exon junction, then Upf1 is thought to elicit NMD by interacting with EJC-associated Upf2 (Maquat, 2004a; Lykke-Andersen et al., 2000; Mendell et al., 2000; Serin et al., 2001). Consistent with a role for EJCs in NMD is the observation that NC-containing mRNAs that derive from intronless genes fail to undergo NMD (Brocke et al., 2002; Maquat and Li, 2001).
Once the mRNA is remodeled so that eukaryotic translation initiation factor (eIF)4E replaces CBP80-CBP20 at the mRNA cap, PABPC replaces PABPN1 at the poly(A) tail, and EJCs have been removed from mRNA, the mRNA becomes immune to NMD (Chiu et al., 2004; Ishigaki et al., 2001; Lejeune et al., 2002). Translation has been reported to remove Y14 (Dostie and Dreyfuss, 2002), and it may remove other mRNA-binding proteins as well. Although these conclusions derive largely from studies of mRNP structure, they are consistent with kinetic analyses indicating that NMD is restricted to newly synthesized mRNA and does not detectably target steady-state mRNA (Belgrader et al., 1994; Cheng and Maquat, 1993; Lejeune et al., 2003).
Cell fractionation studies indicate that most nonsense-containing mRNAs are subject to nucleus-associated NMD (reviewed in Maquat, 2004a). This means that mRNA decay occurs prior to the release of newly synthesized mRNAs into the cytoplasm. Nucleus-associated NMD has been proposed to occur within the nucleoplasm, but it is generally thought to take place during or after mRNA transport across the nuclear pore complex (Dahlberg et al., 2003; Maquat, 2002). A fraction of mRNAs is subject to cytoplasmic NMD (e.g. Dreumont et al., 2004; Moriarty et al., 1998). What destines some mRNAs for nucleus-associated NMD and others for cytoplasmic NMD is currently unknown.
NMD in mammalian cells occurs both 5'-to-3' and 3'-to-5'; it thus involves decapping and 5'-to-3' exonucleolytic activities as well as deadenylating and 3'-to-5' exosomal activities (Lejeune et al., 2003; Chen and Shyu, 2003). It remains to be determined whether NMD occurs in association with translating ribosomes or so-called cytoplasmic foci, which appear to be ribosome-free sites of general mRNA decay (Cougot et al., 2004; Ingelfinger et al., 2002). Notably, the efficiency of NMD in mammalian cells is generally not influenced by NC position, indicating that a higher number of downstream EJCs does not lead to more efficient NMD. However, NMD can be augmented by additional mechanisms that are not well understood. For example, replacing exons 2-4 and flanking intron sequences of the triosephosphate isomerase (TPI) gene with the 383-bp VDJ exon and flanking intron sequences of the T-cell receptor ß (TCR-ß) gene, which generates mRNA that is more efficiently targeted for NMD than TPI mRNA, increases the efficiency with which TPI mRNA undergoes NMD >15-fold (Gudikote and Wilkinson, 2002). The efficiency of NMD is increased only when the TCR-ß sequence is located upstream of an NC.
An understanding of how various factors function in NMD is far from complete. Upf1 is an ATP-dependent group 1 RNA helicase and phosphoprotein (Bhattacharya et al., 2000; Pal et al., 2001; Sun et al., 1998) that, as described above, presumably triggers NMD by interacting with Upf2 at an EJC that resides sufficiently far downstream of an NC. Also, as noted above, Upf2 and either Upf3 or Upf3X, which appear to have distinct but overlapping functions (Lykke-Andersen et al., 2000; Serin et al., 2001; Gehring et al., 2003), are components of the EJC. In fact, Upf3 and Upf3X consist of multiple isoforms that result from alternative pre-mRNA splicing. Whether or not Upf2, Upf3 and Upf3X are involved in Upf1 dephosphorylation, as are their orthologues in C. elegans (Page et al., 1999), remains to be determined. However, as in C. elegans (Grimson et al., 2004; Page et al., 1999), Upf1 phosphorylation is mediated by the PIK-related kinase SMG1 (Brumbaugh et al., 2004; Denning et al., 2001; Yamashita et al., 2001). Also as in C. elegans (Anders et al., 2003; Page et al., 1999) and, possibly, D. melanogaster (Gatfield et al., 2003), Upf1 dephosphorylation is mediated by SMG5 and, presumably, SMG6 and SMG7 (Chiu et al., 2003; Gatfield et al., 2003; Ohnishi et al., 2003).
Interestingly, factors that function in NMD have also been shown to function in other pathways. For example, SMG1 is an ATM-related kinase that is also involved in the recognition and/or repair of damaged DNA (Brumbaugh et al., 2004). SMG1 phosphorylates the tumor suppressor checkpoint protein p53 in response to UV and 
irradiation, and cells in which SMG1 has been downregulated accumulate spontaneous DNA damage and are sensitized to ionizing radiation (Brumbaugh et al., 2004). Providing another example, Upf1 is the 
helicase that partially co-purifies with DNA polymerase (Carastro et al., 2002). Upf1 (unlike Upf2, the only other NMD factor tested) also appears to function in nonsense-mediated altered splicing (NAS), a poorly understood pathway by which NCs influence the efficiency or accuracy of splicing (Mendell et al., 2002; Wang et al., 2002). In fact, Upf1 can be mutated so that it functions in NAS but not NMD (Mendell et al., 2002), indicating that the two pathways are genetically separable. Furthermore, Upf1 has recently been found to function in a new pathway called Staufen 1 (Stau1)-mediated mRNA decay (SMD) (Kim et al., 2005). In this pathway, the RNA-binding protein Stau1 interacts directly with Upf1 to elicit mRNA decay when bound sufficiently far downstream of an NC, including the normal termination codon. The results of microarray analyses indicate that there are a number of natural targets for SMD (Kim et al., 2005). Finally, Upf1 interacts with PABPC and forms distinct complexes of approximately 1.3 MDa and 400-600 kDa that appear to differ in their content (Schell et al., 2003). The functional significance of all these findings remains unknown. Multiple roles for NMD factors are also evident in the case of SMG5, SMG6 and SMG7, which are identical to the Ever Shorter Telomere (EST) proteins EST1B, EST1A and EST1C, respectively (Reichenbach et al., 2003; Snow et al., 2003). Each associates with active telomerase and is involved in telomere integrity (Reichenbach et al., 2003; Snow et al., 2003).
As is evident from this short overview, many mechanistic details of NMD still require resolution. In the future, it will also be important for us to understand the extent to which NMD regulates the level of proper mRNA production as opposed to degrading mRNAs that produce aberrant and, therefore, potentially harmful proteins. How NMD is mechanistically linked to other cellular processes, some of which can also be viewed as a type of quality control, requires further study.
 |
Acknowledgments |
|---|
|
References |
|---|
 Top References |
|---|
Anders, K. R., Grimson, A. and Anderson, P. (2003). SMG-5, required for C. elegans nonsense-mediated mRNA decay, associates with SMG-2 and protein phosphatase 2A. EMBO J. 22, 641-650.[CrossRef][Medline]
Belgrader, P., Cheng, J., Zhou, X., Stephenson, L. S. and Maquat, L. E. (1994). Mammalian nonsense codons can be cis effectors of nuclear mRNA half-life. Mol. Cell. Biol. 14, 8219-8228.
Bhattacharya, A., Czaplinski, K., Trifillis, P., He, F., Jacobson, A. and Peltz, S. W. (2000). Characterization of the biochemical properties of the human Upf1 gene product that is involved in nonsense-mediated mRNA decay. RNA 6, 1226-1235.[Abstract]
Bono, F., Ebert, J., Unterholzner, L., Guttler, T., Izaurralde, E. and Conti, E. (2004). Molecular insights into the interaction of PYM with the Mago-Y14 core of the exon junction complex. EMBO Rep. 5, 304-310.[CrossRef][Medline]
Brocke, K. S., Neu-Yilik, G., Gehring, N. H., Hentze, M. W. and Kulozik, A. E. (2002). The human intronless melanocortin 4-receptor gene is NMD insensitive. Hum. Mol. Genet. 11, 331-335.
Brumbaugh, K. M., Otterness, D. M., Geisen, C., Oliveira, V., Brognard, J., Li, X., Lejeune, F., Maquat, L. E. and Abraham, R. T. (2004). The mRNA surveillance protein, hSMG-1, functions in genotoxic stress response pathways in mammalian cells. Mol. Cell 14, 585-598.[CrossRef][Medline]
Carastro, L. M., Tan, C. K., Selg, M., Jack, H. M., So, A. G. and Downey, K. M. (2002). Identification of delta helicase as the bovine homolog of HUPF1: demonstration of an interaction with the third subunit of DNA polymerase delta. Nucleic Acids Res. 30, 2232-2243.
Chan, C. C., Dostie, J., Diem, M. D., Feng, W., Mann, M., Rappsilber, J. and Dreyfuss, G. (2004). eIF4A3 is a novel component of the exon junction complex. RNA 10, 200-209.
Chen, C. Y. and Shyu, A.-B. (2003). Rapid deadenylation triggered by a nonsense codon precedes decay of the RNA body in a mammalian cytoplasmic nonsense-mediated decay pathway. Mol. Cell. Biol. 23, 4805-4813.
Cheng, J. and Maquat, L. E. (1993). Nonsense codons can reduce the abundance of nuclear mRNA without affecting the abundance of pre-mRNA or the half-life of cytoplasmic mRNA. Mol. Cell. Biol. 13, 1892-1902.
Chiu, S. Y., Serin, G., Ohara, O. and Maquat, L. E. (2003). Characterization of human Smg5/7a: A protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1. RNA 9, 77-87.
Chiu, S. Y., Lejeune, F., Ranganathan, A. C. and Maquat, L. E. (2004). The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex. Genes Dev. 18, 745-754.
Cougot, N., Babajko, S. and Seraphin, B. (2004). Cytoplasmic foci are sites of mRNA decay in human cells. J. Cell. Biol. 165, 31-40.
Custodio, N., Carvalho, C., Condado, I., Antoniou, M., Blencowe, B. J. and Carmo-Fonseca, M. (2004). In vivo recruitment of exon junction complex proteins to transcription sites in mammalian cell nuclei. RNA 10, 622-633.
Dahlberg, J. E., Lund, E. and Goodwin, E. B. (2003). Nuclear translation: what is the evidence? RNA 9, 1-8.
Degot, S., le Hir, H., Alpy, F., Kedinger, V., Stoll, I., Wendling, C., Seraphin, B., Rio, M. C. and Tomasetto, C. (2004). Association of the breast cancer protein MLN51 with the exon junction complex via its speckle localizer and RNA binding module. J Biol. Chem. 279, 33702-33715.
Denning, G., Jamieson, L., Maquat, L. E., Thompson, E. A. and Fields, A. P. (2001). Cloning of a novel phosphatidylinositol kinase-related kinase: characterization of the human SMG-1 RNA surveillance protein. J Biol. Chem. 276, 22709-22714.
Dostie, J. and Dreyfuss, G. (2002). Translation is required to remove Y14 from mRNAs in the cytoplasm. Curr. Biol. 12, 1060-1067.[CrossRef][Medline]
Dreumont, N., Maresca, A., Khandjian, E. W., Baklouti, F. and Tanguay, R. M. (2004). Cytoplasmic nonsense-mediated mRNA decay for a nonsense (W262X) transcript of the gene responsible for hereditary tyrosinemia, fumarylacetoacetate hydrolase. Biochem. Biophys. Res. Commun. 324, 186-192.[CrossRef][Medline]
Ferraiuolo, M. A., Lee, C. S., Ler, L. W., Hsu, J. L., Costa-Mattioli, M., Luo, M. J., Reed, R. and Sonenberg, N. (2004). A nuclear translation-like factor eIF4AIII is recruited to the mRNA during splicing and functions in nonsense-mediated decay. Proc. Natl. Acad. Sci. USA 101, 4118-4123.
Gatfield, D., Unterholzner, L., Ciccarelli, F. D., Bork, P. and Izaurralde, E. (2003). Nonsense-mediated mRNA decay in Drosophila: at the intersection of the yeast and mammalian pathways. EMBO J. 22, 3960-3970.[CrossRef][Medline]
Gehring, N. H., Neu-Yilik, G., Schell. T., Hentze. M. W. and Kulozik, A. E. (2003). Y14 and hUpf3b form an NMD-activating complex. Mol. Cell 11, 939-949.[CrossRef][Medline]
Grimson, A., O'Connor, S., Newman, C. L. and Anderson, P. (2004). SMG-1 is a phosphatidylinositol kinase-related protein kinase required for nonsense-mediated mRNA decay in Caenorhabditis elegans. Mol. Cell. Biol. 24, 7483-7490.
Gudikote, J. P. and Wilkinson, M. F. (2002). T-cell receptor sequences that elicit strong down-regulation of premature termination codon-bearing transcripts. EMBO J. 21, 125-134.[CrossRef][Medline]
Hillman, R. T., Green, R. E. and Brenner, S. E. (2004). An unappreciated role for RNA surveillance. Genome Biol. 5, R8.[CrossRef][Medline]
Ingelfinger, D., Arndt-Jovin, D. J., Luhrmann, R. and Achsel, T. (2002). The human LSm1-7 proteins colocalize with the mRNA-degrading enzymes Dcp1/2 and Xrnl in distinct cytoplasmic foci. RNA 8, 1489-1501.[Abstract]
Ishigaki, Y., Li, X., Serin, G. and Maquat, L. E. (2001). Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20. Cell 106, 607-617.[CrossRef][Medline]
Kadlec, J., Izaurralde, E. and Cusack, S. (2004). The structural basis for the interaction between nonsense-mediated mRNA decay factors UPF2 and UPF3. Nat. Struct. Mol. Biol. 11, 330-337.[CrossRef][Medline]
Kataoka, N., Yong, J., Kim, V. N., Velazquez, F., Perkinson, R. A., Wang, F. and Dreyfuss, G. (2000). Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm. Mol. Cell 6, 673-682.[CrossRef][Medline]
Kim, V. N., Kataoka, N. and Dreyfuss, G. (2001). Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex. Science 293, 1832-1836.
Kim, Y. K., Furic, L., DesGroseillers, L. and Maquat, L. E. (2005). Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay. Cell 120, 195-208.[CrossRef][Medline]
Le Hir, H., Izaurralde, E., Maquat, L. E. and Moore, M. J. (2000a). The spliceosome deposits multiple proteins 20-24 nucleotides upstream of mRNA exon-exon junctions. EMBO J. 19, 6860-6869.[CrossRef][Medline]
Le Hir, H., Moore, M. J. and Maquat, L. E. (2000b). Pre-mRNA splicing alters mRNP composition: evidence for stable association of proteins at exon-exon junctions. Genes Dev. 14, 1098-1108.
Le Hir, H., Gatfield, D., Izaurralde, E. and Moore, M. J. (2001). The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay. EMBO J. 20, 4987-4997.[CrossRef][Medline]
Lejeune, F., Ishigaki, Y., Li, X. and Maquat, L. E. (2002). The exon junction complex is detected on CBP80-bound but not eIF4E-bound mRNA in mammalian cells: dynamics of mRNP remodeling. EMBO J. 21, 3536-3545.[CrossRef][Medline]
Lejeune, F., Li, X. and Maquat, L. E. (2003). Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities. Mol. Cell 12, 675-687.[CrossRef][Medline]
Lejeune, F., Ranganathan, A. C. and Maquat, L. E. (2004). eIF4G is required for the pioneer round of translation in mammalian cells. Nat. Struct. Mol. Biol. 11, 992-1000.[CrossRef][Medline]
Li, C., Lin, R. I., Lai, M. C., Ouyang, P. and Tarn, W. Y. (2003). Nuclear Pnn/DRS protein binds to spliced mRNPs and participates in mRNA processing and export via interaction with RNPS1. Mol. Cell. Biol. 23, 7363-7376.
Luo, M. L., Zhou, Z., Magni, K., Christoforides, C., Rappsilber, J., Mann, M. and Reed, R. (2001). Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. Nature 413, 644-647.[CrossRef][Medline]
Lykke-Andersen, J., Shu, M. D. and Steitz, J. A. (2000). Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon. Cell 103, 1121-1131.[CrossRef][Medline]
Lykke-Andersen, J., Shu, M. D. and Steitz, J. A. (2001). Communication of the position of exon-exon junctions to the mRNA surveillance machinery by the protein RNPS1. Science 293, 1836-1839.
Maquat, L. E. (2002). NASty effects on fibrillin pre-mRNA splicing: another case of ESE does it, but proposals for translation-dependent splice site choice live on. Genes Dev. 16, 1743-1753.
Maquat, L. E. (2004a). Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics. Nat. Rev. Mol. Cell. Biol. 5, 89-99.[CrossRef][Medline]
Maquat, L. E. (2004b). Nonsense-mediated mRNA decay: a comparative analysis of different species. Curr. Genomics 5, 175-190.
Maquat, L. E. and Li, X. (2001). Mammalian heat shock p70 and histone H4 transcripts, which derive from naturally intronless genes, are immune to nonsense-mediated decay. RNA 7, 445-456.[Abstract]
Medghalchi, S. M., Frischmeyer, P. A., Mendell, J. T., Kelly, A. G., Lawler, A. M. and Dietz, H. C. (2001). Rent1, a trans-effector of nonsense-mediated mRNA decay, is essential for mammalian embryonic viability. Hum. Mol. Genet. 10, 99-105.
Mendell, J. T., Medghalchi, S. M., Lake, R. G., Noensie, E. N. and Dietz, H. C. (2000). Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes. Mol. Cell. Biol. 20, 8944-8957.
Mendell, J. T., ap Rhys, C. M. and Dietz, H. C. (2002). Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts. Science 298, 419-422.
Mendell, J. T., Sharifi, N. A., Meyers, J. L., Martinez-Murillo, F. and Dietz, H. C. (2004). Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise. Nat. Genet. 36, 1073-1078.[CrossRef][Medline]
Moriarty, P. M., Reddy, C. C. and Maquat, L. E. (1998). Selenium deficiency reduces the abundance of mRNA for Se-dependent glutathione peroxidase 1 by a UGA-dependent mechanism likely to be nonsense codon-mediated decay of cytoplasmic mRNA. Mol. Cell. Biol. 18, 2932-2939.
Nagy, E. and Maquat, L. E. (1998). A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance. Trends Biochem. Sci. 23, 198-199.[CrossRef][Medline]
Ohnishi, T., Yamashita, A., Kashima, I., Schell, T., Anders, K. R., Grimson, A., Hachiya, T., Hentze, M. W., Anderson, P. and Ohno, S. (2003). Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7. Mol. Cell 12, 1187-1200.[CrossRef][Medline]
Page, M. F., Carr, B., Anders, K. R., Grimson, A. and Anderson, P. (1999). SMG-2 is a phosphorylated protein required for mRNA surveillance in Caenorhabditis elegans and related to Upf1p of yeast. Mol. Cell. Biol. 19, 5943-5951.
Pal, M., Ishigaki, Y., Nagy, E. and Maquat, L. E. (2001). Evidence that phosphorylation of human Upfl protein varies with intracellular location and is mediated by a wortmannin-sensitive and rapamycin-sensitive PI 3-kinase-related kinase signaling pathway. RNA 7, 5-15.[Abstract]
Palacios, I. M., Gatfield, D., St Johnston, D. and Izaurralde, E. (2004). An eIF4AIII-containing complex required for mRNA localization and nonsense-mediated mRNA decay. Nature 427, 753-757.[CrossRef][Medline]
Reichenbach, P., Hoss, M., Azzalin, C. M., Nabholz, M., Bucher, P. and Lingner, J. (2003). A human homolog of yeast Est1 associates with telomerase and uncaps chromosome ends when overexpressed. Curr. Biol. 13, 568-574.[CrossRef][Medline]
Schell, T., Kocher, T., Wilm, M., Seraphin, B., Kulozik, A. E. and Hentze, M. W. (2003). Complexes between the nonsense-mediated mRNA decay pathway factor human upf1 (up-frameshift protein 1) and essential nonsense-mediated mRNA decay factors in HeLa cells. Biochem. J. 373, 775-783.[CrossRef][Medline]
Serin, G., Gersappe, A., Black, J. D., Aronoff, R. and Maquat, L. E. (2001). Identification and characterization of human orthologues to Saccharomyces cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis elegans SMG-4). Mol. Cell. Biol. 21, 209-223.
Shibuya, T., Tange, T. O., Sonenberg, N. and Moore, M. J. (2004). eIF4AIII binds spliced mRNA in the exon junction complex and is essential for nonsense-mediated decay. Nat. Struct. Mol. Biol. 11, 346-351.[CrossRef][Medline]
Snow, B. E., Erdmann, N., Cruickshank, J., Goldman, H., Gill, R. M., Robinson, M. O. and Harrington, L. (2003). Functional conservation of the telomerase protein Est1p in humans. Curr. Biol. 13, 698-704.[CrossRef][Medline]
Sun, X., Perlick, H. A., Dietz, H. C. and Maquat, L. E. (1998). A mutated human homologue to yeast Upf1 protein has a dominant-negative effect on the decay of nonsense-containing mRNAs in mammalian cells. Proc. Natl. Acad. Sci. USA 95, 10009-10014.
Thein, S. L. (2004). Genetic insights into the clinical diversity of beta thalassaemia. Br. J. Haematol. 124, 264-274.[CrossRef][Medline]
Wang, J., Chang, Y. F., Hamilton, J. I. and Wilkinson, M. F. (2002). Nonsense-associated altered splicing: a frame-dependent response distinct from nonsense-mediated decay. Mol. Cell 10, 951-957.[CrossRef][Medline]
Yamashita, A., Ohnishi, T., Kashima, I., Taya, Y. and Ohno, S. (2001). Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay. Genes Dev. 15, 2215-2228.
This article has been cited by other articles:
|
|
 |
|
  C. Dall'Osso, I. Guella, S. Duga, N. Locatelli, E. M. Paraboschi, M. Spreafico, A. Afrasiabi, C. Pechlaner, F. Peyvandi, M. L. Tenchini, et al. Molecular characterization of three novel splicing mutations causing factor V deficiency and analysis of the F5 gene splicing pattern Haematologica, October 1, 2008; 93(10): 1505 - 1513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rajab, D. Kelberman, S. C.P. de Castro, H. Biebermann, H. Shaikh, K. Pearce, C. M. Hall, G. Shaikh, D. Gerrelli, A. Grueters, et al. Novel mutations in LHX3 are associated with hypopituitarism and sensorineural hearing loss Hum. Mol. Genet., July 15, 2008; 17(14): 2150 - 2159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Oliveira, W. J. Romanow, C. Geisen, D. M. Otterness, F. Mercurio, H. G. Wang, W. S. Dalton, and R. T. Abraham A Protective Role for the Human SMG-1 Kinase against Tumor Necrosis Factor-{alpha}-induced Apoptosis J. Biol. Chem., May 9, 2008; 283(19): 13174 - 13184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Mutesa, N. Muganga, W. Lissens, F. Boemer, R. Schoos, G. Pierquin, and V. Bours Molecular Analysis in Two Siblings African Patients with Severe Form of Hunter Syndrome: Identification of a Novel (p.Y54X) Nonsense Mutation J Trop Pediatr, December 1, 2007; 53(6): 434 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Goulet, G. Gauvin, S. Boisvenue, and J. Cote Alternative Splicing Yields Protein Arginine Methyltransferase 1 Isoforms with Distinct Activity, Substrate Specificity, and Subcellular Localization J. Biol. Chem., November 9, 2007; 282(45): 33009 - 33021. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kollberg, M. Tulinius, T. Gilljam, I. Ostman-Smith, G. Forsander, P. Jotorp, A. Oldfors, and E. Holme Cardiomyopathy and Exercise Intolerance in Muscle Glycogen Storage Disease 0 N. Engl. J. Med., October 11, 2007; 357(15): 1507 - 1514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Askew, S. Cataltepe, V. Kumar, C. Edwards, S. M. Pace, R. N. Howarth, S. C. Pak, Y. S. Askew, D. Bromme, C. J. Luke, et al. SERPINB11 Is a New Noninhibitory Intracellular Serpin: COMMON SINGLE NUCLEOTIDE POLYMORPHISMS IN THE SCAFFOLD IMPAIR CONFORMATIONAL CHANGE J. Biol. Chem., August 24, 2007; 282(34): 24948 - 24960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Chauvin, S. Salhi, and O. Jean-Jean Human Eukaryotic Release Factor 3a Depletion Causes Cell Cycle Arrest at G1 Phase through Inhibition of the mTOR Pathway Mol. Cell. Biol., August 15, 2007; 27(16): 5619 - 5629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. N. Kierlin-Duncan and B. A. Sullenger Using 5'-PTMs to repair mutant beta-globin transcripts RNA, August 1, 2007; 13(8): 1317 - 1327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Isken and L. E. Maquat Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function Genes & Dev., August 1, 2007; 21(15): 1833 - 3856. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Barwell, L Pangon, S Hodgson, A Georgiou, I Kesterton, T Slade, M Taylor, S J Payne, H Brinkman, J Smythe, et al. Biallelic mutation of MSH2 in primary human cells is associated with sensitivity to irradiation and altered RAD51 foci kinetics J. Med. Genet., August 1, 2007; 44(8): 516 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Zhang and A. R. Krainer Splicing remodels messenger ribonucleoprotein architecture via eIF4A3-dependent and -independent recruitment of exon junction complex components PNAS, July 10, 2007; 104(28): 11574 - 11579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wu, S. Ren, L. Nguyen, J. S. Adams, and M. Hewison Splice Variants of the CYP27b1 Gene and the Regulation of 1,25-Dihydroxyvitamin D3 Production Endocrinology, July 1, 2007; 148(7): 3410 - 3418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. Coutinho-Mansfield, Y. Xue, Y. Zhang, and X.-D. Fu PTB/nPTB switch: a post-transcriptional mechanism for programming neuronal differentiation Genes & Dev., July 1, 2007; 21(13): 1573 - 1577. [Full Text] [PDF]
|
|
|
|
|
|
P. L. Boutz, P. Stoilov, Q. Li, C.-H. Lin, G. Chawla, K. Ostrow, L. Shiue, M. Ares Jr., and D. L. Black A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons Genes & Dev., July 1, 2007; 21(13): 1636 - 1652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. K. Conrad, M.-D. Shu, K. E. Uyhazi, and J. A. Steitz Mutational analysis of a viral RNA element that counteracts rapid RNA decay by interaction with the polyadenylate tail PNAS, June 19, 2007; 104(25): 10412 - 10417. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Riveira-Munoz, Q. Chang, N. Godefroid, J. G. Hoenderop, R. J. Bindels, K. Dahan, O. Devuyst, and for the Belgian Network for the Study of Gitelman Transcriptional and Functional Analyses of SLC12A3 Mutations: New Clues for the Pathogenesis of Gitelman Syndrome J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1271 - 1283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Z. Ni, L. Grate, J. P. Donohue, C. Preston, N. Nobida, G. O'Brien, L. Shiue, T. A. Clark, J. E. Blume, and M. Ares Jr. Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay Genes & Dev., March 15, 2007; 21(6): 708 - 718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Gunnarsson, A. R. Hellstrom, M. Tixier-Boichard, F. Minvielle, B. Bed'hom, S. Ito, P. Jensen, A. Rattink, A. Vereijken, and L. Andersson Mutations in SLC45A2 Cause Plumage Color Variation in Chicken and Japanese Quail Genetics, February 1, 2007; 175(2): 867 - 877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Banihashemi, G. M. Wilson, N. Das, and G. Brewer Upf1/Upf2 Regulation of 3' Untranslated Region Splice Variants of AUF1 Links Nonsense-Mediated and A+U-Rich Element-Mediated mRNA Decay Mol. Cell. Biol., December 1, 2006; 26(23): 8743 - 8754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Y. Morozov, S. Negrete-Urtasun, J. Tilburn, C. A. Jansen, M. X. Caddick, and H. N. Arst Jr. Nonsense-Mediated mRNA Decay Mutation in Aspergillus nidulans Eukaryot. Cell, November 1, 2006; 5(11): 1838 - 1846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Vorechovsky Aberrant 3' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization Nucleic Acids Res., September 15, 2006; (2006) gkl535v2. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Buratti, M. Baralle, and F. E. Baralle Defective splicing, disease and therapy: searching for master checkpoints in exon definition Nucleic Acids Res., July 19, 2006; 34(12): 3494 - 3510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Okada, Y. Ishii, K. Masujin, A. Yasoshima, J. Matsuda, A. Ogura, H. Nakayama, T. Kunieda, and K. Doi The Critical Roles of Serum/Glucocorticoid-Regulated Kinase 3 (SGK3) in the Hair Follicle Morphogenesis and Homeostasis: The Allelic Difference Provides Novel Insights into Hair Follicle Biology Am. J. Pathol., April 1, 2006; 168(4): 1119 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. SHIBUYA, T. O. TANGE, M. E. STROUPE, and M. J. MOORE Mutational analysis of human eIF4AIII identifies regions necessary for exon junction complex formation and nonsense-mediated mRNA decay. RNA, March 1, 2006; 12(3): 360 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Khan, K.-S. Oh, T. Shahlavi, T. Ueda, D. B. Busch, H. Inui, S. Emmert, K. Imoto, V. Muniz-Medina, C. C. Baker, et al. Reduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma pigmentosum patients Carcinogenesis, January 1, 2006; 27(1): 84 - 94. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||
