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NAM7  -  ATP-dependent RNA helicase NAM7

Saccharomyces cerevisiae S288c

Synonyms: ATP-dependent helicase NAM7, IFS2, MOF4, Nonsense-mediated mRNA decay protein 1, Nuclear accommodation of mitochondria 7 protein, ...
 
 
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High impact information on NAM7

  • Conversely, a uORF-containing mRNA that lacks an STE, such as CPA1, is degraded by the NMD pathway [1].
  • Transcripts containing mutations that insert an upstream open reading frame (uORF) in the 5'-UTR are degraded through NMD [1].
  • In yeast, the products of the UPF1 and UPF3 genes are required for this decay pathway, and in this report we focus on the identification and characterization of additional factors required for rapid decay of nonsense-containing mRNAs [2].
  • In this paper we report the identification and characterization of NMD2, a yeast gene that encodes a specific Upf1p-interacting protein [3].
  • Screening of yeast genomic libraries identified six genes encoding potential Upf1p-interacting proteins [3].
 

Biological context of NAM7

  • However as for many mitochondrial genes, ISF1 expression is sensitive to fermentative repression; in contrast expression of the NAM7 gene is unaffected by glucose [4].
  • We propose that ISF1 could influence the NAM7/UPF1 function, possibly at the level of mRNA turnover, thus modulating the expression of nuclear genes involved in mitochondrial biogenesis [4].
  • The participation of the NMD factors in general mRNA degradation suggests that they may regulate an aspect of translation termination common to all transcripts [5].
  • We propose a model in which the NMD pathway regulates the levels of specific mRNAs that are important for telomere functions [6].
  • Upf1p control of nonsense mRNA translation is regulated by Nmd2p and Upf3p [7].
 

Anatomical context of NAM7

  • Nonsense-mediated mRNA decay (NMD) is a conserved proofreading mechanism that protects eukaryotic cells from the potentially deleterious effects of truncated proteins [8].
  • In addition, we show that, when overexpressed, Upf1p is not detected within mitochondria, suggesting that its role as multicopy suppressor of mitochondrial splicing deficiency is indirect [9].
  • Analyses of chimeric mRNAs used to identify the cis-acting basis for NMD of the SPT10 mRNA indicated that ribosomes scan beyond its initiator AUG and initiate at the next downstream AUG, resulting in premature translation termination [10].
  • Using monkey COS cells and human HeLa cells, we demonstrate that expression of human Upf1 protein harboring an arginine-to-cysteine mutation at residue 844 within the RNA helicase domain acts in a dominant-negative fashion to abrogate the decay of nonsense-containing mRNA that takes place (i) in association with nuclei or (ii) in the cytoplasm [11].
  • Dbp2p, like Upf1p, acts before or at decapping, is predominantly cytoplasmic, and associates with polyribosomes [12].
 

Associations of NAM7 with chemical compounds

  • Mutations in the conserved cysteine- and histidine-rich regions and ATPase and helicase motifs of Upf1p separate the ability of Upf1p to complement the respiratory impairment of a Deltaupf1 strain from its ability to act as a multicopy suppressor of mitochondrial splicing deficiency, indicating that distinct pathways express these phenotypes [9].
  • Our results indicate that the NMD destabilizes the 5' end of the CPA1 message and this decay is strongly enhanced when arginine is present in the growth medium [13].
  • The mof4-1 strain is more sensitive to the aminoglycoside antibiotic paromomycin than a upf1 delta strain, and frameshifting efficiency increases in a mof4-1 strain grown in the presence of this drug [14].
  • In this report, we describe the identification and biochemical characterization of mutations in the amino-terminal cysteine- and histidine-rich region of Upf1p that have normal nonsense-mediated mRNA decay activities but are able to suppress leu2-2 and tyr7-1 nonsense alleles [15].
  • Accelerated turnover via this pathway required Upf1p and was blocked by the translation inhibitor cycloheximide [16].
 

Physical interactions of NAM7

  • We showed previously that Upf1p and Nmd2p interact and that this interaction is required for nonsense-mediated mRNA decay (F. He and A. Jacobson, Genes Dev. 9:437-454, 1995; F. He, A. H. Brown, and A. Jacobson, RNA 2:153-170, 1996) [17].
  • A mutation in HRP1 that stabilizes nonsense-containing mRNAs abolishes its affinity for the DSE and fails to interact with Upf1p [18].
  • Nup100p and Nup116p can be co-immunoprecipitated from whole-cell extracts with Upf1p, confirming in vitro the interaction identified by the two-hybrid analysis [19].
  • NMD can trigger decay during any round of translation and can target Cbc-bound or eIF-4E-bound transcripts [20].
  • We have mapped an Upf1p-dependent destabilizing element to a region located within the 5'-UTR and the first 92 bases of the PPR1 ORF [21].
 

Enzymatic interactions of NAM7

  • Southern blot analysis of DNA extracted from a nam7 :: URA3 deleted strain revealed the presence of a second gene whose sequence is related to that of the NAM7 gene and which could participate in the same process [22].
 

Regulatory relationships of NAM7

  • We propose that NAM7 is under the control of a negative Cyp1p-dependent regulator and that its absence favours a transcriptional read-through which results in the ISF1-NAM7 cotranscript we have identified [23].
  • Here we describe the identification and characterization of the Hrp1/Nab4 protein as a DSE-binding factor that activates NMD [18].
  • The half-life of STN1 mRNA was not altered in upf mutant strains, suggesting that an NMD-controlled transcription factor regulates the levels of STN1 mRNA [24].
  • Further, the results indicate that the STE functions in the context of the GCN4 transcript to inactivate the NMD pathway [25].
  • Translation of two-thirds of the PGK1 coding region inactivates the nonsense-mediated mRNA decay pathway [26].
 

Other interactions of NAM7

  • Our results indicate that Upf1p, Nmd2p, and Upf3p regulate decapping and exonucleolytic degradation of nonsense-containing mRNAs [5].
  • The two adjacent nuclear genes ISF1 and NAM7 cooperatively participate in mitochondrial functions [23].
  • In addition, a significant amount of ISF1-NAM7 cotranscript is observed in a cyp1 mutant context [23].
  • In the absence of UPF1 function, frameshift or nonsense mutations in the HIS4 or LEU2 genes that normally cause rapid mRNA decay fail to have this effect [27].
  • The growth and mRNA decay defects of ts942 (grc5) cells were suppressed by overexpression of the NMD3 gene, encoding a protein shown to participate in a two-hybrid interaction with the nonsense-mediated decay protein Upf1p [28].
 

Analytical, diagnostic and therapeutic context of NAM7

  • Although such transcripts are generally degraded by nonsense-mediated mRNA decay (NMD), it was established by real-time PCR quantification that the ATP7A(Delta ex3+ex4) transcript was protected from degradation [29].

References

  1. The RNA binding protein Pub1 modulates the stability of transcripts containing upstream open reading frames. Ruiz-Echevarría, M.J., Peltz, S.W. Cell (2000) [Pubmed]
  2. Identification and characterization of genes that are required for the accelerated degradation of mRNAs containing a premature translational termination codon. Cui, Y., Hagan, K.W., Zhang, S., Peltz, S.W. Genes Dev. (1995) [Pubmed]
  3. Identification of a novel component of the nonsense-mediated mRNA decay pathway by use of an interacting protein screen. He, F., Jacobson, A. Genes Dev. (1995) [Pubmed]
  4. Two adjacent nuclear genes, ISF1 and NAM7/UPF1, cooperatively participate in mitochondrial functions in Saccharomyces cerevisiae. Altamura, N., Dujardin, G., Groudinsky, O., Slonimski, P.P. Mol. Gen. Genet. (1994) [Pubmed]
  5. Upf1p, Nmd2p, and Upf3p regulate the decapping and exonucleolytic degradation of both nonsense-containing mRNAs and wild-type mRNAs. He, F., Jacobson, A. Mol. Cell. Biol. (2001) [Pubmed]
  6. Telomere length regulation and telomeric chromatin require the nonsense-mediated mRNA decay pathway. Lew, J.E., Enomoto, S., Berman, J. Mol. Cell. Biol. (1998) [Pubmed]
  7. Upf1p control of nonsense mRNA translation is regulated by Nmd2p and Upf3p. Maderazo, A.B., He, F., Mangus, D.A., Jacobson, A. Mol. Cell. Biol. (2000) [Pubmed]
  8. Nonsense-containing mRNAs that accumulate in the absence of a functional nonsense-mediated mRNA decay pathway are destabilized rapidly upon its restitution. Maderazo, A.B., Belk, J.P., He, F., Jacobson, A. Mol. Cell. Biol. (2003) [Pubmed]
  9. Overexpression of Upf1p compensates for mitochondrial splicing deficiency independently of its role in mRNA surveillance. de Pinto, B., Lippolis, R., Castaldo, R., Altamura, N. Mol. Microbiol. (2004) [Pubmed]
  10. An internal open reading frame triggers nonsense-mediated decay of the yeast SPT10 mRNA. Welch, E.M., Jacobson, A. EMBO J. (1999) [Pubmed]
  11. A mutated human homologue to yeast Upf1 protein has a dominant-negative effect on the decay of nonsense-containing mRNAs in mammalian cells. Sun, X., Perlick, H.A., Dietz, H.C., Maquat, L.E. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  12. Absence of Dbp2p alters both nonsense-mediated mRNA decay and rRNA processing. Bond, A.T., Mangus, D.A., He, F., Jacobson, A. Mol. Cell. Biol. (2001) [Pubmed]
  13. Role of RNA surveillance proteins Upf1/CpaR, Upf2 and Upf3 in the translational regulation of yeast CPA1 gene. Messenguy, F., Vierendeels, F., Piérard, A., Delbecq, P. Curr. Genet. (2002) [Pubmed]
  14. Mof4-1 is an allele of the UPF1/IFS2 gene which affects both mRNA turnover and -1 ribosomal frameshifting efficiency. Cui, Y., Dinman, J.D., Peltz, S.W. EMBO J. (1996) [Pubmed]
  15. Identification and characterization of mutations in the UPF1 gene that affect nonsense suppression and the formation of the Upf protein complex but not mRNA turnover. Weng, Y., Czaplinski, K., Peltz, S.W. Mol. Cell. Biol. (1996) [Pubmed]
  16. An NMD pathway in yeast involving accelerated deadenylation and exosome-mediated 3'-->5' degradation. Mitchell, P., Tollervey, D. Mol. Cell (2003) [Pubmed]
  17. Upf1p, Nmd2p, and Upf3p are interacting components of the yeast nonsense-mediated mRNA decay pathway. He, F., Brown, A.H., Jacobson, A. Mol. Cell. Biol. (1997) [Pubmed]
  18. The yeast hnRNP-like protein Hrp1/Nab4 marks a transcript for nonsense-mediated mRNA decay. González, C.I., Ruiz-Echevarría, M.J., Vasudevan, S., Henry, M.F., Peltz, S.W. Mol. Cell (2000) [Pubmed]
  19. Upf1p, a highly conserved protein required for nonsense-mediated mRNA decay, interacts with the nuclear pore proteins Nup100p and Nup116p. Nazarenus, T., Cedarberg, R., Bell, R., Cheatle, J., Forch, A., Haifley, A., Hou, A., Wanja Kebaara, B., Shields, C., Stoysich, K., Taylor, R., Atkin, A.L. Gene (2005) [Pubmed]
  20. Transcript selection and the recruitment of mRNA decay factors for NMD in Saccharomyces cerevisiae. Culbertson, M.R., Neeno-Eckwall, E. RNA (2005) [Pubmed]
  21. The Upf-dependent decay of wild-type PPR1 mRNA depends on its 5'-UTR and first 92 ORF nucleotides. Kebaara, B., Nazarenus, T., Taylor, R., Forch, A., Atkin, A.L. Nucleic Acids Res. (2003) [Pubmed]
  22. NAM7 nuclear gene encodes a novel member of a family of helicases with a Zn-ligand motif and is involved in mitochondrial functions in Saccharomyces cerevisiae. Altamura, N., Groudinsky, O., Dujardin, G., Slonimski, P.P. J. Mol. Biol. (1992) [Pubmed]
  23. The transcription of NAM7/UPF1 is enhanced in the absence of Cyp1p/Hap1p concomitant with the appearance of an ISF1-NAM7 cotranscript in Saccharomyces cerevisiae. Altamura, N., de Pinto, B., Castaldo, R., Verdiére, J. FEBS Lett. (1997) [Pubmed]
  24. mRNAs encoding telomerase components and regulators are controlled by UPF genes in Saccharomyces cerevisiae. Dahlseid, J.N., Lew-Smith, J., Lelivelt, M.J., Enomoto, S., Ford, A., Desruisseaux, M., McClellan, M., Lue, N., Culbertson, M.R., Berman, J. Eukaryotic Cell (2003) [Pubmed]
  25. Identifying the right stop: determining how the surveillance complex recognizes and degrades an aberrant mRNA. Ruiz-Echevarría, M.J., González, C.I., Peltz, S.W. EMBO J. (1998) [Pubmed]
  26. Characterization of cis-acting sequences and decay intermediates involved in nonsense-mediated mRNA turnover. Hagan, K.W., Ruiz-Echevarria, M.J., Quan, Y., Peltz, S.W. Mol. Cell. Biol. (1995) [Pubmed]
  27. The product of the yeast UPF1 gene is required for rapid turnover of mRNAs containing a premature translational termination codon. Leeds, P., Peltz, S.W., Jacobson, A., Culbertson, M.R. Genes Dev. (1991) [Pubmed]
  28. Temperature-sensitive mutations in the Saccharomyces cerevisiae MRT4, GRC5, SLA2 and THS1 genes result in defects in mRNA turnover. Zuk, D., Belk, J.P., Jacobson, A. Genetics (1999) [Pubmed]
  29. Evidence that translation reinitiation leads to a partially functional Menkes protein containing two copper-binding sites. Paulsen, M., Lund, C., Akram, Z., Winther, J.R., Horn, N., Møller, L.B. Am. J. Hum. Genet. (2006) [Pubmed]
 
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