The Yeast La Related Protein Slf1p Is a Key Activator of Translation during the Oxidative Stress Response


All organisms must respond to changes in their external environment such as exposure to different stresses. The availability of genome sequences and post-genomic technologies has enabled the analysis of these adaptive responses at the molecular level in terms of altered gene expression profiles. However, relatively few studies have focused on how cells regulate the translation of mRNA into protein in response to stress, despite its fundamental role in gene expression pathways. In this study, we show that a previously identified RNA-binding protein called Slf1p plays a major role in mRNA-specific regulation of translation during oxidative stress conditions and is necessary to promote the translation of stress-responsive mRNAs. This protein is a member of the so-called “La-related” family of proteins that have not been well characterized, although they are conserved throughout evolution. Exposure to oxidants is known to cause a general down-regulation of protein synthesis, although many stress response proteins are able to overcome this inhibition and increase their protein levels following stress by as yet unknown mechanisms. Our experiments offer one possible explanation, as they show that Slf1p plays a critical role in enhancing translation of many of these proteins, including many that are necessary for the cellular stress response.


Vyšlo v časopise: The Yeast La Related Protein Slf1p Is a Key Activator of Translation during the Oxidative Stress Response. PLoS Genet 11(1): e32767. doi:10.1371/journal.pgen.1004903
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004903

Souhrn

All organisms must respond to changes in their external environment such as exposure to different stresses. The availability of genome sequences and post-genomic technologies has enabled the analysis of these adaptive responses at the molecular level in terms of altered gene expression profiles. However, relatively few studies have focused on how cells regulate the translation of mRNA into protein in response to stress, despite its fundamental role in gene expression pathways. In this study, we show that a previously identified RNA-binding protein called Slf1p plays a major role in mRNA-specific regulation of translation during oxidative stress conditions and is necessary to promote the translation of stress-responsive mRNAs. This protein is a member of the so-called “La-related” family of proteins that have not been well characterized, although they are conserved throughout evolution. Exposure to oxidants is known to cause a general down-regulation of protein synthesis, although many stress response proteins are able to overcome this inhibition and increase their protein levels following stress by as yet unknown mechanisms. Our experiments offer one possible explanation, as they show that Slf1p plays a critical role in enhancing translation of many of these proteins, including many that are necessary for the cellular stress response.


Zdroje

1. VogelC, MarcotteEM (2012) Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nature Reviews Genetics 13: 227–232.

2. SchwanhaeusserB, BusseD, LiN, DittmarG, SchuchhardtJ, et al. (2011) Global quantification of mammalian gene expression control. Nature 473: 337–342.

3. SimpsonCE, AsheMP (2012) Adaptation to stress in yeast: to translate or not? Biochemical Society Transactions 40: 794–799.

4. JacksonRJ, HellenCUT, PestovaTV (2010) The mechanism of eukaryotic translation initiation and principles of its regulation. Nature Reviews Molecular Cell Biology 11: 113–127.

5. Tsvetanova NG, Klass DM, Salzman J, Brown PO (2010) Proteome-Wide Search Reveals Unexpected RNA-Binding Proteins in Saccharomyces cerevisiae. Plos One 5.

6. Bousquet-AntonelliC, DeragonJ-M (2009) A comprehensive analysis of the La-motif protein superfamily. Rna-a Publication of the Rna Society 15: 750–764.

7. BayfieldMA, YangR, MaraiaRJ (2010) Conserved and divergent features of the structure and function of La and La-related proteins (LARPs). Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms 1799: 365–378.

8. YangR, GaidamakovSA, XieJ, LeeJ, MartinoL, et al. (2011) La-Related Protein 4 Binds Poly(A), Interacts with the Poly(A)-Binding Protein MLLE Domain via a Variant PAM2w Motif, and Can Promote mRNA Stability. Molecular and Cellular Biology 31: 542–556.

9. AokiK, AdachiS, HomotoM, KusanoH, KoikeK, et al. (2013) LARP1 specifically recognizes the 3 ′ terminus of poly(A) mRNA. Febs Letters 587: 2173–2178.

10. SobelSG, WolinSL (1999) Two yeast La motif-containing proteins are RNA-binding proteins that associate with polyribosomes. Molecular Biology of the Cell 10: 3849–3862.

11. SchaefflerK, SchulzK, HirmerA, WiesnerJ, GrimmM, et al. (2010) A stimulatory role for the La-related protein 4B in translation. Rna-a Publication of the Rna Society 16: 1488–1499.

12. SchenkL, MeinelDM, StraesserK, GerberAP (2012) La-motif-dependent mRNA association with Slf1 promotes copper detoxification in yeast. Rna-a Publication of the Rna Society 18: 449–461.

13. Chatenay-Lapointe M, Shadel GS (2011) Repression of Mitochondrial Translation, Respiration and a Metabolic Cycle-Regulated Gene, SLF1, by the Yeast Pumilio-Family Protein Puf3p. Plos One 6.

14. KeeneJD (2007) RNA regulons: coordination of post-transcriptional events. Nature Reviews Genetics 8: 533–543.

15. ShentonD, SmirnovaJB, SelleyJN, CarrollK, HubbardSJ, et al. (2006) Global translational responses to oxidative stress impact upon multiple levels of protein synthesis. Journal of Biological Chemistry 281: 29011–29021.

16. SubtelnyAO, EichhornSW, ChenGR, SiveH, BartelDP (2014) Poly(A)-tail profiling reveals an embryonic switch in translational control. Nature 508: 66–71.

17. YuW, FarrellRA, StillmanDJ, WingeDR (1996) Identification of SLF1 as a new copper homeostasis gene involved in copper sulfide mineralization in Saccharomyces cerevisiae. Molecular and Cellular Biology 16: 2464–2472.

18. GaschAP, SpellmanPT, KaoCM, Carmel-HarelO, EisenMB, et al. (2000) Genomic expression programs in the response of yeast cells to environmental changes. Molecular Biology of the Cell 11: 4241–4257.

19. MascarenhasC, Edwards-IngramLC, ZeefL, ShentonD, AsheMP, et al. (2008) Gcn4 is required for the response to peroxide stress in the yeast Saccharomyces cerevisiae. Molecular Biology of the Cell 19: 2995–3007.

20. WellsSE, HillnerPE, ValeRD, SachsAB (1998) Circularization of mRNA by eukaryotic translation initiation factors. Molecular Cell 2: 135–140.

21. RichardsonR, DenisCL, ZhangC, NielsenMEO, ChiangY-C, et al. (2012) Mass spectrometric identification of proteins that interact through specific domains of the poly(A) binding protein. Molecular Genetics and Genomics 287: 711–730.

22. DavidA, NetzerN, StraderMB, DasSR, ChenCY, et al. (2011) RNA Binding Targets Aminoacyl-tRNA Synthetases to Translating Ribosomes. Journal of Biological Chemistry 286: 20688–20700.

23. Lui J, Castelli LM, Pizzinga M, Simpson CE, Hoyle NP, et al. (2014) Granules harboring translationally active mRNAs provide a platform for P-body formation following stress (In Press). Cell Reports.

24. DongG, ChakshusmathiG, WolinSL, ReinischKM (2004) Structure of the La motif: a winged helix domain mediates RNA binding via a conserved aromatic patch. Embo Journal 23: 1000–1007.

25. WangM, WeissM, SimonovicM, HaertingerG, SchrimpfSP, et al. (2012) PaxDb, a Database of Protein Abundance Averages Across All Three Domains of Life. Molecular & Cellular Proteomics 11: 492–500.

26. CridgeAG, CastelliLM, SmirnovaJB, SelleyJN, RoweW, et al. (2010) Identifying eIF4E-binding protein translationally-controlled transcripts reveals links to mRNAs bound by specific PUF proteins. Nucleic Acids Research 38: 8039–8050.

27. AltmannM, SonenbergN, TrachselH (1989) TRANSLATION IN SACCHAROMYCES-CEREVISIAE - INITIATION-FACTOR 4E-DEPENDENT CELL-FREE SYSTEM. Molecular and Cellular Biology 9: 4467–4472.

28. ArmacheJ-P, JaraschA, AngerAM, VillaE, BeckerT, et al. (2010) Cryo-EM structure and rRNA model of a translating eukaryotic 80S ribosome at 5.5-angstrom resolution. Proceedings of the National Academy of Sciences of the United States of America 107: 19748–19753.

29. ArmacheJ-P, JaraschA, AngerAM, VillaE, BeckerT, et al. (2010) Localization of eukaryote-specific ribosomal proteins in a 5.5-angstrom cryo-EM map of the 80S eukaryotic ribosome. Proceedings of the National Academy of Sciences of the United States of America 107: 19754–19759.

30. BaumS, BittinsM, FreyS, SeedorfM (2004) Asc1p, a WD40-domain containing adaptor protein, is required for the interaction of the RNA-binding protein Scp160p with polysomes. Biochemical Journal 380: 823–830.

31. SezenB, SeedorfM, SchiebelE (2009) The SESA network links duplication of the yeast centrosome with the protein translation machinery. Genes & Development 23: 1559–1570.

32. GerashchenkoMV, LobanovAV, GladyshevVN (2012) Genome-wide ribosome profiling reveals complex translational regulation in response to oxidative stress. Proceedings of the National Academy of Sciences of the United States of America 109: 17394–17399.

33. TcherkezianJ, CargnelloM, RomeoY, HuttlinEL, LavoieG, et al. (2014) Proteomic analysis of cap-dependent translation identifies LARP1 as a key regulator of 5 ′ TOP mRNA translation. Genes & Development 28: 357–371.

34. SenguptaJ, AgrawalRK, FrankJ (2001) Visualization of protein S1 within the 30S ribosomal subunit and its interaction with messenger RNA. Proceedings of the National Academy of Sciences of the United States of America 98: 11991–11996.

35. DuttaguptaR, TianB, WiluszCJ, KhounhDT, SoteropoulosP, et al. (2005) Global analysis of Pup1p targets reveals a coordinate control of gene expression through modulation of binding and stability. Molecular and Cellular Biology 25: 5499–5513.

36. HoganD, RiordanD, GerberA, HerschlagD, BrownP (2008) Diverse RNA-Binding Proteins Interact with Functionally Related Sets of RNAs, Suggesting an Extensive Regulatory System. Plos Biology 6: 2297–2313.

37. KunkelTA (1985) RAPID AND EFFICIENT SITE-SPECIFIC MUTAGENESIS WITHOUT PHENOTYPIC SELECTION. Proceedings of the National Academy of Sciences of the United States of America 82: 488–492.

38. TaylorEJ, CampbellSG, GriffithsCD, ReidPJ, SlavenJW, et al. (2010) Fusel Alcohols Regulate Translation Initiation by Inhibiting eIF2B to Reduce Ternary Complex in a Mechanism That May Involve Altering the Integrity and Dynamics of the eIF2B Body. Molecular Biology of the Cell 21: 2202–2216.

39. TrotterEW, RandJD, VickerstaffJ, GrantCM (2008) The yeast Tsa1 peroxiredoxin is a ribosome-associated antioxidant. Biochemical Journal 412: 73–80.

40. RoweW, KershawCJ, CastelliLM, CostelloJL, AsheMP, et al. (2014) Puf3p induces translational repression of genes linked to oxidative stress. Nucleic Acids Research 42: 1026–1041.

41. RobinsonMD, McCarthyDJ, SmythGK (2010) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26: 139–140.

42. McCarthyDJ, ChenY, SmythGK (2012) Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Research 40: 4288–4297.

43. BaileyTL, BodenM, BuskeFA, FrithM, GrantCE, et al. (2009) MEME SUITE: tools for motif discovery and searching. Nucleic Acids Research 37: W202–W208.

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Genetika Reprodukčná medicína

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