Skip to main content
SpringerLink
Log in

tRNA Misacylation with Methionine in the Mouse Gut Microbiome in Situ

  • Note
  • Published:
Microbial Ecology Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Global protein mistranslation with methionine has been shown to be a conserved biological process that affords distinct functional advantages in all three domains of life. In all instances, methionine mistranslation occurs through a regulated process where low-fidelity forms of methionyl-tRNA synthetase are conditionally induced to mischarge non-methionyl-tRNAs with methionine followed by the utilization of the misacylated tRNAs in translation. In mammals, methionine mistranslation contributes to oxidative stress response; in the hyperthermophilic archaeon Aeropyrum pernix, methionine mistranslation produces proteins that are better adapted to low temperature growth; in E. coli, methionine mistranslation increases resistance to antibiotics and chemical stressors. The phenotypic benefits conferred by tRNA mismethionylation suggest that it should be a widespread adaptational mechanism in diverse bacterial lineages, yet this response has only been described in E. coli. Furthermore, previous microbial investigations on this response have been confined to axenic laboratory cultures. It was unknown whether tRNA mismethionylation was relevant in a natural microbial habitat. Here we show that four abundant gut microbiotal genera belonging to the Firmicutes and Bacteroidetes phyla perform constitutive tRNA misacylation with methionine in the mouse cecum in situ. These results reveal the ubiquity of the tRNA mismethionylation process among bacteria and implicate the potential importance of this response for subsistence and adaptation in natural habitats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  1. Netzer N, Goodenbour JM, David A, Dittmar KA, Jones RB, Schneider JR, Boone D, Eves EM, Rosner MR, Gibbs JS, Embry A, Dolan B, Das S, Hickman HD, Berglund P, Bennink JR, Yewdell JW, Pan T (2009) Innate immune and chemically triggered oxidative stress modifies translational fidelity. Nature 462:522–526. doi:10.1038/nature08576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Schwartz MH, Pan T (2016) Temperature dependent mistranslation in a hyperthermophile adapts proteins to lower temperatures. Nucleic Acids Res. 44:294–303. doi:10.1093/nar/gkv1379

    Article  CAS  PubMed  Google Scholar 

  3. Wiltrout E, Goodenbour JM, Frechin M, Pan T (2012) Misacylation of tRNA with methionine in Saccharomyces cerevisiae. Nucleic Acids Res. 40:10494–10506. doi:10.1093/nar/gks805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lee JY, Kim DG, Kim BG, Yang WS, Hong J, Kang T, Oh YS, Kim KR, Han BW, Hwang BJ, Kang BS, Kang MS, Kim MH, Kwon NH, Kim S (2014) Promiscuous methionyl-tRNA synthetase mediates adaptive mistranslation to protect cells against oxidative stress. J. Cell Sci. 127:4234–4245. doi:10.1242/jcs.152470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Schwartz MH, Waldbauer JR, Zhang L, Pan T (2016) Global tRNA misacylation induced by anaerobiosis and antibiotic exposure broadly increases stress resistance in Escherichia coli. Nucleic Acids Res. doi:10.1093/nar/gkw856

    Google Scholar 

  6. Wang X, Pan T (2015) Methionine mistranslation bypasses the restraint of the genetic code to generate mutant proteins with distinct activities. PLoS Genet. 11:e1005745. doi:10.1371/journal.pgen.1005745

    Article  PubMed  PubMed Central  Google Scholar 

  7. Savage DC (1977) Microbial ecology of the gastrointestinal tract. Annu. Rev. Microbiol. 31:107–133. doi:10.1146/annurev.mi.31.100177.000543

    Article  CAS  PubMed  Google Scholar 

  8. Flint HJ, Scott KP, Louis P, Duncan SH (2012) The role of the gut microbiota in nutrition and health. Nat. Rev. Gastroenterol. Hepatol. 9:577–589. doi:10.1038/nrgastro.2012.156

    Article  CAS  PubMed  Google Scholar 

  9. Consortium THMP (2012) Structure, function and diversity of the healthy human microbiome. Nature 486:207–214. doi:10.1038/nature11234

    Article  Google Scholar 

  10. Weinstock GM (2012) Genomic approaches to studying the human microbiota. Nature 489:250–256. doi:10.1038/nature11553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Walker AW, Duncan SH, Louis P, Flint HJ (2014) Phylogeny, culturing, and metagenomics of the human gut microbiota. Trends Microbiol. 22:267–274. doi:10.1016/j.tim.2014.03.001

    Article  CAS  PubMed  Google Scholar 

  12. Schwartz MH, Pan T (2016) Determining the fidelity of tRNA aminoacylation via microarrays. Methods. doi:10.1016/j.ymeth.2016.09.004

    PubMed  Google Scholar 

  13. Dittmar KA, Mobley EM, Radek AJ, Pan T (2004) Exploring the regulation of tRNA distribution on the genomic scale. J. Mol. Biol. 337:31–47. doi:10.1016/j.jmb.2004.01.024

    Article  CAS  PubMed  Google Scholar 

  14. Dittmar KA, Goodenbour JM, Pan T (2006) Tissue-specific differences in human transfer RNA expression. PLoS Genet. 2:e221. doi:10.1371/journal.pgen.0020221

    Article  PubMed  PubMed Central  Google Scholar 

  15. Nguyen TL, Vieira-Silva S, Liston A, Raes J (2015) How informative is the mouse for human gut microbiota research? Disease models & mechanisms 8:1–16. doi:10.1242/dmm.017400

    Article  CAS  Google Scholar 

  16. Chan PP, Lowe TM (2009) GtRNAdb: a database of transfer RNA genes detected in genomic sequence. Nucleic Acids Res. 37:D93–D97. doi:10.1093/nar/gkn787

    Article  CAS  PubMed  Google Scholar 

  17. Wattam AR, Abraham D, Dalay O, Disz TL, Driscoll T, Gabbard JL, Gillespie JJ, Gough R, Hix D, Kenyon R, Machi D, Mao C, Nordberg EK, Olson R, Overbeek R, Pusch GD, Shukla M, Schulman J, Stevens RL, Sullivan DE, Vonstein V, Warren A, Will R, Wilson MJ, Yoo HS, Zhang C, Zhang Y, Sobral BW (2014) PATRIC, the bacterial bioinformatics database and analysis resource. Nucleic Acids Res. 42:D581–D591. doi:10.1093/nar/gkt1099

    Article  CAS  PubMed  Google Scholar 

  18. Flint HJ, Duncan SH, Scott KP, Louis P (2007) Interactions and competition within the microbial community of the human colon: links between diet and health. Environ. Microbiol. 9:1101–1111. doi:10.1111/j.1462-2920.2007.01281.x

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Brian Cheng for providing access to fresh mouse cecum. This work was supported by the NIH MCB Training Grant (T32 GM007183) to M.S. and the NIH Director’s Pioneer Award (DP1GM105386) to T.P.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, 60637, USA

    Michael H. Schwartz & Tao Pan

  2. Committee on Microbiology, University of Chicago, Chicago, IL, 60637, USA

    Michael H. Schwartz & Tao Pan

Authors
  1. Michael H. Schwartz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tao Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Michael H. Schwartz or Tao Pan.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Figure S1

Array probe design for tRNAMets. To minimize false positives derived from tRNAMets beyond the 4 bacterial genera, tRNAMet probes were expanded to 10 major genera known to be present in the mouse gut microbiome (panel A; [15]). The number of sequence differences of initiator or formyl-tRNAMet (iMet, panel B) and the elongator tRNAMet (eMet, panel C) between these genera are shown. Since the resolution of our array method is ~8 nucleotides, some array probes represent tRNAMet from more than one genus. Six probes were used for iMet (i1-i6), and 12 probes were used for eMet (e1-e12). tRNAs with similar sequences to be detected by a combined probe are boxed together. (PDF 53 kb)

Table S1

Sequences of all 192 probes used for the microbiome array. (XLS 53 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schwartz, M.H., Pan, T. tRNA Misacylation with Methionine in the Mouse Gut Microbiome in Situ. Microb Ecol 74, 10–14 (2017). https://doi.org/10.1007/s00248-016-0928-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00248-016-0928-0

Keywords

Search

Navigation