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Gene Review

XRN1  -  Xrn1p

Saccharomyces cerevisiae S288c

Synonyms: 5'-3' exoribonuclease 1, DNA strand transfer protein beta, DST2, G1645, KAR(-)-enhancing mutation protein, ...
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Disease relevance of KEM1

  • Furthermore, the overexpression of the ROK1 gene, which directly binds to Osh3p, conferred resistance against ISP-1, and the deletion of the KEM1 gene, which regulates microtubule functions, exhibited ISP-1 hypersensitivity [1].
  • We propose that Li+ toxicity in yeast is due to synthetic lethality evoked between Xrn1p and RNase MRP [2].

High impact information on KEM1

  • Other genes in the second cluster, which are required for G1-S progression, are regulated by the MBF complex independently of Sep1p and Ace2p [3].
  • Since a homozygous deletion of the KEM1 gene blocks meiotic cells at the 4N stage, the finding of these G4-dependent DNA binding and cleavage activities for the KEM1 gene product supports the hypothesis that G4-DNA may play a role in meiosis [4].
  • Most CUP1 transcripts made by DeltaCTD Pol II were degraded but could be stabilized by deletion of the XRN1 gene [5].
  • In addition, in cells deleted for the XRN1 gene, which encodes a major 5' to 3' exonuclease in yeast, the MFA2 transcript is deadenylated normally but persists as a full-length mRNA lacking the 5' cap structure [6].
  • We discuss the possible significance of the Rat1p/Sep1p homology for RNA trafficking [7].

Biological context of KEM1


Anatomical context of KEM1

  • Multiple roles for the in vivo function of Sep1, ranging from DNA recombination and cytoskeleton to RNA turnover, have been proposed [13].
  • In xrn1 delta cells, PGK1 transcripts lacking the 5' cap structure and a few nucleotides at the 5' end were detected after deadenylation [14].

Associations of KEM1 with chemical compounds


Physical interactions of KEM1

  • High-copy expression of a mutant eIF4G defective for eIF4E binding resulted in a dominant negative phenotype in an xrn1 mutant, indicating the importance of this interaction in an xrn1 mutant [18].

Regulatory relationships of KEM1

  • Inhibition of mRNA turnover in yeast by an xrn1 mutation enhances the requirement for eIF4E binding to eIF4G and for proper capping of transcripts by Ceg1p [18].
  • The ROK1 gene was initially identified by its ability on a high-copy number plasmid to suppress the nuclear fusion defect caused by the kem1 null mutation [19].
  • Here we report that pAp accumulation in HAL2 mutants inhibits the 5'-->3' exoribonucleases Xrn1p and Rat1p [2].
  • First, an Mr 34,000 single-stranded DNA binding protein stimulated the reaction by lowering the requirement for SEP1 about 3-4 fold [20].
  • Many of these genes are regulated by a transcriptional cascade involving two transcription factors: the forkhead protein Sep1p which activates the zinc finger protein Ace2p [21].

Other interactions of KEM1

  • Three Tn10LUK insertion mutations in the SEP1 gene were characterized. sep1 mutants grew more slowly than wild-type cells, showed a two- to fivefold decrease in the rate of spontaneous mitotic recombination between his4 heteroalleles, and were delayed in their ability to return to growth after UV or gamma irradiation [22].
  • We propose that Sep1/Xrn1 and Ski2 both act to block translation on transcripts targeted for degradation [23].
  • The SEP1 gene mapped to chromosome VII within 20 kbp of RAD54 [22].
  • Thus, the inhibition of mRNA turnover by blocking Xrn1p function does not suppress the lethality of defects upstream in the turnover pathway but it does enhance the requirement for (7)mG caps and for proper formation of the eIF4E/eIF4G cap recognition complex [18].
  • ROK1 is essential for viability and is closely linked to KEM1 on chromosome VII [10].

Analytical, diagnostic and therapeutic context of KEM1


  1. Deletion of OSH3 gene confers resistance against ISP-1 in Saccharomyces cerevisiae. Yano, T., Inukai, M., Isono, F. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  2. Lithium toxicity in yeast is due to the inhibition of RNA processing enzymes. Dichtl, B., Stevens, A., Tollervey, D. EMBO J. (1997) [Pubmed]
  3. Periodic gene expression program of the fission yeast cell cycle. Rustici, G., Mata, J., Kivinen, K., Lió, P., Penkett, C.J., Burns, G., Hayles, J., Brazma, A., Nurse, P., Bähler, J. Nat. Genet. (2004) [Pubmed]
  4. The yeast KEM1 gene encodes a nuclease specific for G4 tetraplex DNA: implication of in vivo functions for this novel DNA structure. Liu, Z., Gilbert, W. Cell (1994) [Pubmed]
  5. Activated transcription independent of the RNA polymerase II holoenzyme in budding yeast. McNeil, J.B., Agah, H., Bentley, D. Genes Dev. (1998) [Pubmed]
  6. Deadenylation of the unstable mRNA encoded by the yeast MFA2 gene leads to decapping followed by 5'-->3' digestion of the transcript. Muhlrad, D., Decker, C.J., Parker, R. Genes Dev. (1994) [Pubmed]
  7. Isolation and characterization of RAT1: an essential gene of Saccharomyces cerevisiae required for the efficient nucleocytoplasmic trafficking of mRNA. Amberg, D.C., Goldstein, A.L., Cole, C.N. Genes Dev. (1992) [Pubmed]
  8. An essential yeast gene with homology to the exonuclease-encoding XRN1/KEM1 gene also encodes a protein with exoribonuclease activity. Kenna, M., Stevens, A., McCammon, M., Douglas, M.G. Mol. Cell. Biol. (1993) [Pubmed]
  9. Structure of the yeast TAP1 protein: dependence of transcription activation on the DNA context of the target gene. Aldrich, T.L., Di Segni, G., McConaughy, B.L., Keen, N.J., Whelen, S., Hall, B.D. Mol. Cell. Biol. (1993) [Pubmed]
  10. ROK1, a high-copy-number plasmid suppressor of kem1, encodes a putative ATP-dependent RNA helicase in Saccharomyces cerevisiae. Song, Y., Kim, S., Kim, J. Gene (1995) [Pubmed]
  11. The sequence of an 11.1 kb fragment on the left arm of Saccharomyces cerevisiae chromosome VII reveals six open reading frames including NSP49, KEM1 and four putative new genes. Bertani, I., Coglievina, M., Zaccaria, P., Klima, R., Bruschi, C.V. Yeast (1995) [Pubmed]
  12. Identification of an exoribonuclease homolog, CaKEM1/CaXRN1, in Candida albicans and its characterization in filamentous growth. An, H.S., Lee, K.H., Kim, J. FEMS Microbiol. Lett. (2004) [Pubmed]
  13. Regulation and intracellular localization of Saccharomyces cerevisiae strand exchange protein 1 (Sep1/Xrn1/Kem1), a multifunctional exonuclease. Heyer, W.D., Johnson, A.W., Reinhart, U., Kolodner, R.D. Mol. Cell. Biol. (1995) [Pubmed]
  14. Turnover mechanisms of the stable yeast PGK1 mRNA. Muhlrad, D., Decker, C.J., Parker, R. Mol. Cell. Biol. (1995) [Pubmed]
  15. A role of Sep1 (= Kem1, Xrn1) as a microtubule-associated protein in Saccharomyces cerevisiae. Interthal, H., Bellocq, C., Bähler, J., Bashkirov, V.I., Edelstein, S., Heyer, W.D. EMBO J. (1995) [Pubmed]
  16. Glucose-dependent turnover of the mRNAs encoding succinate dehydrogenase peptides in Saccharomyces cerevisiae: sequence elements in the 5' untranslated region of the Ip mRNA play a dominant role. Cereghino, G.P., Atencio, D.P., Saghbini, M., Beiner, J., Scheffler, I.E. Mol. Biol. Cell (1995) [Pubmed]
  17. Sodium-induced GCN4 expression controls the accumulation of the 5' to 3' RNA degradation inhibitor, 3'-phosphoadenosine 5'-phosphate. Todeschini, A.L., Condon, C., Bénard, L. J. Biol. Chem. (2006) [Pubmed]
  18. Inhibition of mRNA turnover in yeast by an xrn1 mutation enhances the requirement for eIF4E binding to eIF4G and for proper capping of transcripts by Ceg1p. Brown, J.T., Yang, X., Johnson, A.W. Genetics (2000) [Pubmed]
  19. Two-hybrid cloning and characterization of OSH3, a yeast oxysterol-binding protein homolog. Park, Y.U., Hwang, O., Kim, J. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  20. Saccharomyces cerevisiae proteins involved in hybrid DNA formation in vitro. Heyer, W.D., Johnson, A.W., Norris, D.N., Tishkoff, D., Kolodner, R.D. Biochimie (1991) [Pubmed]
  21. A transcriptional pathway for cell separation in fission yeast. Bähler, J. Cell Cycle (2005) [Pubmed]
  22. Molecular and genetic analysis of the gene encoding the Saccharomyces cerevisiae strand exchange protein Sep1. Tishkoff, D.X., Johnson, A.W., Kolodner, R.D. Mol. Cell. Biol. (1991) [Pubmed]
  23. Synthetic lethality of sep1 (xrn1) ski2 and sep1 (xrn1) ski3 mutants of Saccharomyces cerevisiae is independent of killer virus and suggests a general role for these genes in translation control. Johnson, A.W., Kolodner, R.D. Mol. Cell. Biol. (1995) [Pubmed]
  24. The Sep1 strand exchange protein from Saccharomyces cerevisiae promotes a paranemic joint between homologous DNA molecules. Chen, J., Kanaar, R., Cozzarelli, N.R. Genes Dev. (1994) [Pubmed]
  25. Characterization of the interaction of Saccharomyces cerevisiae strand exchange protein 1 with DNA. Johnon, A.W., Kolodner, R.D. J. Biol. Chem. (1994) [Pubmed]
  26. Disruption of the gene XRN1, coding for a 5'----3' exoribonuclease, restricts yeast cell growth. Larimer, F.W., Stevens, A. Gene (1990) [Pubmed]
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