• Integrating tRNA gene epigenom...

Treffer: Integrating tRNA gene epigenomics and expression with codon usage unravels an intricate connection with translatome dynamics in Trypanosoma cruzi .

Title:
Integrating tRNA gene epigenomics and expression with codon usage unravels an intricate connection with translatome dynamics in Trypanosoma cruzi .
Authors:
Silva HGS; Laboratório Ciclo Celular, Instituto Butantan, São Paulo, Brazil.; Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina da Universidade Federal de São Paulo, São Paulo, Brazil., Kimura S; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA.; Department of Microbiology & Immunology, Cornell University College of Veterinary Medicine, Ithaca, New York, USA., Lima PLC; Laboratório Ciclo Celular, Instituto Butantan, São Paulo, Brazil.; Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina da Universidade Federal de São Paulo, São Paulo, Brazil., Pires DS; Laboratório Ciclo Celular, Instituto Butantan, São Paulo, Brazil., Waldor MK; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA., da Cunha JPC; Laboratório Ciclo Celular, Instituto Butantan, São Paulo, Brazil.; Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina da Universidade Federal de São Paulo, São Paulo, Brazil.
Source:
MBio [mBio] 2025 Sep 10; Vol. 16 (9), pp. e0162225. Date of Electronic Publication: 2025 Aug 11.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE
Imprint Name(s):
Original Publication: Washington, D.C. : American Society for Microbiology
MeSH Terms:
Trypanosoma cruzi*/genetics , RNA, Transfer*/genetics , Codon Usage* , Protein Biosynthesis* , Epigenesis, Genetic*, Anticodon/genetics ; Codon ; Ribosomes
References:
Nucleic Acids Res. 2015 Mar 31;43(6):3022-32. (PMID: 25765653)
Elife. 2018 Mar 15;7:. (PMID: 29543155)
Nat Cell Biol. 2024 Jan;26(1):100-112. (PMID: 38191669)
Front Genet. 2017 Jul 19;8:100. (PMID: 28769976)
RNA. 2012 Jul;18(7):1358-72. (PMID: 22586155)
EMBO Rep. 2000 Jul;1(1):18-23. (PMID: 11256617)
FEBS Lett. 2009 Jan 22;583(2):437-42. (PMID: 19114040)
Epigenetics Chromatin. 2020 Apr 22;13(1):21. (PMID: 32321568)
Nat Microbiol. 2023 Nov;8(11):2103-2114. (PMID: 37828247)
J Biochem. 1990 Feb;107(2):242-7. (PMID: 2361955)
J Biol Chem. 1990 Nov 5;265(31):19208-15. (PMID: 2229071)
Front Mol Biosci. 2023 Jul 04;10:1218518. (PMID: 37469707)
DNA Res. 2014 Oct;21(5):511-26. (PMID: 24906480)
Mol Biochem Parasitol. 1985 Sep;16(3):315-27. (PMID: 3903496)
Nucleic Acids Res. 2006;34(21):6137-46. (PMID: 17088292)
Cell Commun Signal. 2020 Sep 9;18(1):145. (PMID: 32907610)
Nucleic Acids Res. 1987 Feb 11;15(3):1281-95. (PMID: 3547335)
Nat Chem Biol. 2020 Sep;16(9):964-972. (PMID: 32514182)
Genome Biol Evol. 2025 May 30;17(6):. (PMID: 40545894)
Mol Biochem Parasitol. 2010 Jun;171(2):64-73. (PMID: 20156490)
Bioinformatics. 2014 Aug 1;30(15):2114-20. (PMID: 24695404)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Nat Biotechnol. 2016 May;34(5):525-7. (PMID: 27043002)
Comput Struct Biotechnol J. 2021 Apr 22;19:2646-2663. (PMID: 34025951)
Nucleic Acids Res. 2013 Jul;41(12):e121. (PMID: 23598997)
Nucleic Acids Res. 2011 May;39(10):4023-34. (PMID: 21266479)
Bull Soc Chim Biol (Paris). 1964;46:1399-425. (PMID: 14270536)
Cell. 2009 Jul 23;138(2):215-9. (PMID: 19632169)
Gene. 2014 Feb 25;536(2):376-84. (PMID: 24342656)
Nat Protoc. 2012 Jan 19;7(2):256-67. (PMID: 22262007)
Mol Cell. 2024 Jan 4;84(1):94-106. (PMID: 38181765)
Open Biol. 2019 Jun 28;9(6):190072. (PMID: 31164043)
Proc Natl Acad Sci U S A. 1964 Jun;51:1134-41. (PMID: 14215634)
PLoS Genet. 2009 Jul;5(7):e1000556. (PMID: 19593368)
Genes (Basel). 2024 Mar 19;15(3):. (PMID: 38540433)
Elife. 2018 Mar 15;7:. (PMID: 29543152)
Mol Cell. 2021 Apr 15;81(8):1802-1815.e7. (PMID: 33581077)
BMC Genomics. 2009 May 18;10:232. (PMID: 19450263)
Biochim Biophys Acta Gene Regul Mech. 2018 Apr;1861(4):295-309. (PMID: 29313808)
J Mol Biol. 1968 Dec;38(3):367-79. (PMID: 4887876)
Proc Natl Acad Sci U S A. 2021 Oct 19;118(42):. (PMID: 34642250)
PLoS Pathog. 2021 Jan 26;17(1):e1009272. (PMID: 33497423)
Nucleic Acids Res. 2020 Oct 9;48(18):10297-10312. (PMID: 32941623)
RNA. 2023 Aug;29(8):1243-1254. (PMID: 37197826)
Open Biol. 2021 Nov;11(11):210190. (PMID: 34753322)
Nat Commun. 2020 Aug 14;11(1):4104. (PMID: 32796835)
RNA Biol. 2018;15(4-5):537-553. (PMID: 28812932)
PLoS Genet. 2016 May 11;12(5):e1006024. (PMID: 27166679)
Glycobiology. 2015 Nov;25(11):1142-9. (PMID: 26224786)
RNA Biol. 2017 Sep 2;14(9):1124-1137. (PMID: 27791472)
Nucleic Acids Res. 2004 Sep 24;32(17):5036-44. (PMID: 15448185)
J Mol Biol. 1966 Aug;19(2):548-55. (PMID: 5969078)
Genes (Basel). 2022 Dec 22;14(1):. (PMID: 36672768)
Nat Methods. 2012 Mar 04;9(4):357-9. (PMID: 22388286)
Proteomics. 2012 Aug;12(17):2694-703. (PMID: 22761176)
BMC Genomics. 2015 Jun 09;16:443. (PMID: 26054634)
Biochim Biophys Acta Gene Regul Mech. 2018 Apr;1861(4):320-329. (PMID: 29378333)
Int J Biol Sci. 2023 Feb 13;19(4):1146-1162. (PMID: 36923941)
Sci Rep. 2017 Apr 7;7(1):723. (PMID: 28389662)
Glob Med Genet. 2021 Sep;8(3):109-115. (PMID: 34430963)
Mol Microbiol. 2017 Feb;103(3):452-468. (PMID: 27802583)
J Exp Clin Cancer Res. 2018 May 9;37(1):101. (PMID: 29743091)
Genome Biol. 2019 Sep 13;20(1):198. (PMID: 31519205)
Nucleic Acids Res. 2009 Nov;37(21):7268-80. (PMID: 19783824)
Genome Res. 2007 Jun;17(6):877-85. (PMID: 17179217)
Sci Signal. 2018 Sep 04;11(546):. (PMID: 30181241)
Nat Rev Mol Cell Biol. 2018 Jan;19(1):20-30. (PMID: 29018283)
Biochem J. 2022 Feb 17;479(4):561-580. (PMID: 35136964)
DNA Res. 2017 Dec 1;24(6):623-633. (PMID: 28992099)
Cell. 2016 Jun 2;165(6):1416-1427. (PMID: 27259150)
Epigenetics Chromatin. 2022 Jun 1;15(1):22. (PMID: 35650626)
Bioinformatics. 2009 Aug 15;25(16):2078-9. (PMID: 19505943)
Nature. 1953 Apr 25;171(4356):737-8. (PMID: 13054692)
Nucleic Acids Res. 2021 Sep 20;49(16):9077-9096. (PMID: 34417604)
Bioinformatics. 2017 Jan 1;33(1):139-141. (PMID: 27634950)
Rev Inst Med Trop Sao Paulo. 1964 May-Jun;6:93-100. (PMID: 14177814)
Bioessays. 2019 May;41(5):e1900009. (PMID: 31026340)
Bioinformatics. 2018 Sep 15;34(18):3094-3100. (PMID: 29750242)
FASEB J. 1993 Jan;7(1):54-63. (PMID: 8422975)
Bioinformatics. 2010 Mar 15;26(6):841-2. (PMID: 20110278)
Nucleic Acids Res. 2012 Nov 1;40(20):10053-63. (PMID: 22941644)
J Mol Biol. 1990 Oct 5;215(3):403-10. (PMID: 2231712)
Int J Cell Biol. 2010;2010:. (PMID: 20811486)
Science. 2025 Mar 07;387(6738):eadn2623. (PMID: 40048539)
Grant Information:
18/15553-9,13/07467-1, 21/11419-9,2020/02708-4 Fundação de Amparo à Pesquisa do Estado de São Paulo; Conselho Nacional de Desenvolvimento Científico e Tecnológico
Contributed Indexing:
Keywords: Trypanosoma; anticodon-codon; codon usage; codon-anticodon; epigenetics; gene regulation; posttranscriptional control mechanisms; protein regulation; tRNA; translatome
Substance Nomenclature:
9014-25-9 (RNA, Transfer)
0 (Anticodon)
0 (Codon)
Entry Date(s):
Date Created: 20250811 Date Completed: 20250910 Latest Revision: 20250912
Update Code:
20250912
PubMed Central ID:
PMC12421993
DOI:
10.1128/mbio.01622-25
PMID:
40788054
Database:
MEDLINE

Weitere Informationen

Codon usage bias impacts protein expression across all kingdoms of life, including trypanosomatids. These protozoa, such as the Trypanosoma cruzi , primarily regulate their protein-coding genes through posttranscriptional mechanisms. Here, we integrated codon usage analyses with translatome data to investigate whether codon bias affects translated transcript expression levels in T. cruzi life forms. For the first time in trypanosomatids, tRNA sequencing was employed to reveal coadaptation between codon usage and anticodon availability. Despite notable differences in the proteomes of infective and noninfective forms, they exhibited similar pools of tRNAs and similar codon usage preferences, with notable differences in A-site ribosome occupancies. We developed pipelines to measure the adaptation of codons to their corresponding tRNA abundance pool (GM-tECA-Geometric Mean of tRNA Expression-Codon Adaptation) and to calculate the percentage of anticodon:codon base pairing modes in the T. cruzi genome. Our pipelines revealed an association between tRNA abundance, anticodon:codon pairing modes, and translated transcript levels. Highly expressed mRNAs are more adapted to tRNA abundance and favor either Watson-Crick or inosine pairing, whereas less expressed mRNAs exhibit lower adaptation to tRNA abundance and enrichment of codon with Wobble (G:U) pairing. Additionally, we observed that open chromatin levels of tRNA genes correlate with tRNA expression in noninfective forms, but not in infective forms, suggesting chromatin states do not control the tRNA pool in the latter. Overall, our findings suggest that protein expression in T. cruzi life forms is influenced by a combination of codon usage bias, tRNA abundance, and anticodon:codon pairing modes, but differences in ribosome A-site occupancies between life forms likely reflect additional layers of translation regulation.
Importance: Trypanosomatids primarily regulate protein expression at the posttranscriptional level, with codon bias playing a crucial role in controlling protein production across all life forms. This study investigated how codon usage, tRNA abundance, and codon pairing modes influence protein production in T. cruzi . Through tRNA sequencing and the integration of epigenomic and translatome data, we discovered that infective and noninfective forms of T. cruzi exhibit similar codon usage and tRNA pool preferences, despite having different proteomes. We developed pipelines applicable to any organism to measure codon adaptation to tRNA pools and pairing modes. Our analysis revealed that highly expressed genes are better aligned with more abundant tRNAs and favor Watson-Crick or inosine pairing. These findings suggest an additional layer of gene regulation based on tRNA availability and pairing modes, which impacts protein expression in the different life forms of T. cruzi .

The authors declare no conflict of interest.