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. 1996 Oct 1;93(20):10928–10932. doi: 10.1073/pnas.93.20.10928

Mammalian orthologues of a yeast regulator of nonsense transcript stability.

H A Perlick 1, S M Medghalchi 1, F A Spencer 1, R J Kendzior Jr 1, H C Dietz 1
PMCID: PMC38260  PMID: 8855285

Abstract

All eukaryotes that have been studied to date possess the ability to detect and degrade transcripts that contain a premature signal for the termination of translation. This process of nonsense-mediated RNA decay has been most comprehensively studied in the yeast Saccharomyces cerevisiae where at least three trans-acting factors (Upf1p through Upf3P) are required. We have cloned cDNAs encoding human and murine homologues of Upf1p, termed rent1 (regulator of nonsense transcripts). Rent1 is the first identified mammalian protein that contains all of the putative functional elements in Upf1p including zinc finger-like and NTPase domains, as well as all motifs common to members of helicase superfamily I. Moreover, expression of a chimeric protein, N and C termini of Upf1p, complements the Upf1p-deficient phenotype in yeast. Thus, despite apparent differences between yeast and mammalian nonsense-mediated RNA decay, these data suggest that the two pathways use functionally related machinery.

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Selected References

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  1. Altschul S. F., Boguski M. S., Gish W., Wootton J. C. Issues in searching molecular sequence databases. Nat Genet. 1994 Feb;6(2):119–129. doi: 10.1038/ng0294-119. [DOI] [PubMed] [Google Scholar]
  2. Aoufouchi S., Yélamos J., Milstein C. Nonsense mutations inhibit RNA splicing in a cell-free system: recognition of mutant codon is independent of protein synthesis. Cell. 1996 May 3;85(3):415–422. doi: 10.1016/s0092-8674(00)81119-8. [DOI] [PubMed] [Google Scholar]
  3. Atkin A. L., Altamura N., Leeds P., Culbertson M. R. The majority of yeast UPF1 co-localizes with polyribosomes in the cytoplasm. Mol Biol Cell. 1995 May;6(5):611–625. doi: 10.1091/mbc.6.5.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bassett D. E., Jr, Boguski M. S., Spencer F., Reeves R., Goebl M., Hieter P. Comparative genomics, genome cross-referencing and XREFdb. Trends Genet. 1995 Sep;11(9):372–373. doi: 10.1016/s0168-9525(00)89109-x. [DOI] [PubMed] [Google Scholar]
  5. Bergeron D., Beauseigle D., Bellemare G. Sequence and expression of a gene encoding a protein with RNA-binding and glycine-rich domains in Brassica napus. Biochim Biophys Acta. 1993 Oct 19;1216(1):123–125. doi: 10.1016/0167-4781(93)90047-h. [DOI] [PubMed] [Google Scholar]
  6. Calvert I., Peng Z. Q., Kung H. F., Raziuddin Cloning and characterization of a novel sequence-specific DNA-binding protein recognizing the negative regulatory element (NRE) region of the HIV-1 long terminal repeat. Gene. 1991 May 30;101(2):171–176. doi: 10.1016/0378-1119(91)90408-4. [DOI] [PubMed] [Google Scholar]
  7. Casari G., Andrade M. A., Bork P., Boyle J., Daruvar A., Ouzounis C., Schneider R., Tamames J., Valencia A., Sander C. Challenging times for bioinformatics. Nature. 1995 Aug 24;376(6542):647–648. doi: 10.1038/376647a0. [DOI] [PubMed] [Google Scholar]
  8. Casari G., De Daruvar A., Sander C., Schneider R. Bioinformatics and the discovery of gene function. Trends Genet. 1996 Jul;12(7):244–245. doi: 10.1016/0168-9525(96)30057-7. [DOI] [PubMed] [Google Scholar]
  9. Catron K. M., Zhang H., Marshall S. C., Inostroza J. A., Wilson J. M., Abate C. Transcriptional repression by Msx-1 does not require homeodomain DNA-binding sites. Mol Cell Biol. 1995 Feb;15(2):861–871. doi: 10.1128/mcb.15.2.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Czaplinski K., Weng Y., Hagan K. W., Peltz S. W. Purification and characterization of the Upf1 protein: a factor involved in translation and mRNA degradation. RNA. 1995 Aug;1(6):610–623. [PMC free article] [PubMed] [Google Scholar]
  11. DeAngelo D. J., DeFalco J., Rybacki L., Childs G. The embryonic enhancer-binding protein SSAP contains a novel DNA-binding domain which has homology to several RNA-binding proteins. Mol Cell Biol. 1995 Mar;15(3):1254–1264. doi: 10.1128/mcb.15.3.1254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. DeMarini D. J., Winey M., Ursic D., Webb F., Culbertson M. R. SEN1, a positive effector of tRNA-splicing endonuclease in Saccharomyces cerevisiae. Mol Cell Biol. 1992 May;12(5):2154–2164. doi: 10.1128/mcb.12.5.2154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Delattre O., Zucman J., Plougastel B., Desmaze C., Melot T., Peter M., Kovar H., Joubert I., de Jong P., Rouleau G. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature. 1992 Sep 10;359(6391):162–165. doi: 10.1038/359162a0. [DOI] [PubMed] [Google Scholar]
  14. Dietz H. C., Kendzior R. J., Jr Maintenance of an open reading frame as an additional level of scrutiny during splice site selection. Nat Genet. 1994 Oct;8(2):183–188. doi: 10.1038/ng1094-183. [DOI] [PubMed] [Google Scholar]
  15. Dietz H. C., Valle D., Francomano C. A., Kendzior R. J., Jr, Pyeritz R. E., Cutting G. R. The skipping of constitutive exons in vivo induced by nonsense mutations. Science. 1993 Jan 29;259(5095):680–683. doi: 10.1126/science.8430317. [DOI] [PubMed] [Google Scholar]
  16. Koonin E. V. A new group of putative RNA helicases. Trends Biochem Sci. 1992 Dec;17(12):495–497. doi: 10.1016/0968-0004(92)90338-a. [DOI] [PubMed] [Google Scholar]
  17. Kozak M. An analysis of vertebrate mRNA sequences: intimations of translational control. J Cell Biol. 1991 Nov;115(4):887–903. doi: 10.1083/jcb.115.4.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Leeds P., Peltz S. W., Jacobson A., Culbertson M. R. The product of the yeast UPF1 gene is required for rapid turnover of mRNAs containing a premature translational termination codon. Genes Dev. 1991 Dec;5(12A):2303–2314. doi: 10.1101/gad.5.12a.2303. [DOI] [PubMed] [Google Scholar]
  19. Leeds P., Wood J. M., Lee B. S., Culbertson M. R. Gene products that promote mRNA turnover in Saccharomyces cerevisiae. Mol Cell Biol. 1992 May;12(5):2165–2177. doi: 10.1128/mcb.12.5.2165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Maquat L. E. When cells stop making sense: effects of nonsense codons on RNA metabolism in vertebrate cells. RNA. 1995 Jul;1(5):453–465. [PMC free article] [PubMed] [Google Scholar]
  21. Mooslehner K., Müller U., Karls U., Hamann L., Harbers K. Structure and expression of a gene encoding a putative GTP-binding protein identified by provirus integration in a transgenic mouse strain. Mol Cell Biol. 1991 Feb;11(2):886–893. doi: 10.1128/mcb.11.2.886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mumberg D., Müller R., Funk M. Regulatable promoters of Saccharomyces cerevisiae: comparison of transcriptional activity and their use for heterologous expression. Nucleic Acids Res. 1994 Dec 25;22(25):5767–5768. doi: 10.1093/nar/22.25.5767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Naeger L. K., Schoborg R. V., Zhao Q., Tullis G. E., Pintel D. J. Nonsense mutations inhibit splicing of MVM RNA in cis when they interrupt the reading frame of either exon of the final spliced product. Genes Dev. 1992 Jun;6(6):1107–1119. doi: 10.1101/gad.6.6.1107. [DOI] [PubMed] [Google Scholar]
  24. Pulak R., Anderson P. mRNA surveillance by the Caenorhabditis elegans smg genes. Genes Dev. 1993 Oct;7(10):1885–1897. doi: 10.1101/gad.7.10.1885. [DOI] [PubMed] [Google Scholar]
  25. Seipel K., Georgiev O., Schaffner W. Different activation domains stimulate transcription from remote ('enhancer') and proximal ('promoter') positions. EMBO J. 1992 Dec;11(13):4961–4968. doi: 10.1002/j.1460-2075.1992.tb05603.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ursic D., Culbertson M. R. The yeast homolog to mouse Tcp-1 affects microtubule-mediated processes. Mol Cell Biol. 1991 May;11(5):2629–2640. doi: 10.1128/mcb.11.5.2629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zhong T., Arndt K. T. The yeast SIS1 protein, a DnaJ homolog, is required for the initiation of translation. Cell. 1993 Jun 18;73(6):1175–1186. doi: 10.1016/0092-8674(93)90646-8. [DOI] [PubMed] [Google Scholar]

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