Treffer: Unconventional codon usage bias mediates mRNA translational dynamics in macrophages.
Title:
Unconventional codon usage bias mediates mRNA translational dynamics in macrophages.
Authors:
Luo S; Department of Urology of The Second Affiliated Hospital of Medicine & Liangzhu Laboratory, College of Animal Sciences, Zhejiang University, Hangzhou, China.; Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, China., Wang Q; Department of Urology of The Second Affiliated Hospital of Medicine & Liangzhu Laboratory, College of Animal Sciences, Zhejiang University, Hangzhou, China., Chen A; Department of Urology of The Second Affiliated Hospital of Medicine & Liangzhu Laboratory, College of Animal Sciences, Zhejiang University, Hangzhou, China., Huang L; Department of Urology of The Second Affiliated Hospital of Medicine & Liangzhu Laboratory, College of Animal Sciences, Zhejiang University, Hangzhou, China.; Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, China., Liu Y; Institute of Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou, China., Zong X; Department of Urology of The Second Affiliated Hospital of Medicine & Liangzhu Laboratory, College of Animal Sciences, Zhejiang University, Hangzhou, China.; Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, China., Mao Y; Department of Urology of The Second Affiliated Hospital of Medicine & Liangzhu Laboratory, College of Animal Sciences, Zhejiang University, Hangzhou, China.
Source:
PLoS biology [PLoS Biol] 2025 Sep 18; Vol. 23 (9), pp. e3003403. Date of Electronic Publication: 2025 Sep 18 (Print Publication: 2025).
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: eCollection Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE
Imprint Name(s):
Original Publication: San Francisco, CA : Public Library of Science, [2003]-
MeSH Terms:
Macrophages*/metabolism , Macrophages*/drug effects , RNA, Messenger*/genetics , RNA, Messenger*/metabolism , Protein Biosynthesis*/genetics , Codon Usage*/genetics, Animals ; Mice ; Lipopolysaccharides/pharmacology ; Mice, Inbred C57BL ; 5' Untranslated Regions/genetics ; Gene Expression Regulation ; Codon/genetics ; Cytokines/metabolism
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Cell Death Differ. 2002 Feb;9(2):99-100. (PMID: 11840159)
Nature. 2019 Oct;574(7779):575-580. (PMID: 31645732)
J Mol Evol. 1986;24(1-2):28-38. (PMID: 3104616)
Nucleic Acids Res. 2020 Feb 20;48(3):1029-1042. (PMID: 31504789)
Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):E6117-E6126. (PMID: 28696283)
Genome Res. 2024 Apr 25;34(3):394-409. (PMID: 38508694)
Immunity. 2016 Mar 15;44(3):450-462. (PMID: 26982353)
Genome Biol. 2023 Feb 24;24(1):34. (PMID: 36829202)
Nucleic Acids Res. 2012 Nov 1;40(20):10053-63. (PMID: 22941644)
Nat Immunol. 2015 Aug;16(8):838-849. (PMID: 26147685)
Annu Rev Physiol. 2017 Feb 10;79:567-592. (PMID: 27959619)
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Mol Cell Proteomics. 2014 Mar;13(3):792-810. (PMID: 24396086)
Curr Opin Immunol. 2014 Feb;26:41-8. (PMID: 24556399)
PLoS Biol. 2006 Jun;4(6):e180. (PMID: 16700628)
J Immunol. 2006 Oct 1;177(7):4907-16. (PMID: 16982933)
J Immunol. 2006 Feb 15;176(4):2219-28. (PMID: 16455978)
Mol Immunol. 2017 Oct;90:42-49. (PMID: 28697404)
Nature. 2023 Sep;621(7978):423-430. (PMID: 37674078)
J Immunol. 2008 Sep 15;181(6):3733-9. (PMID: 18768823)
Mol Immunol. 2013 Mar;53(3):179-86. (PMID: 22944456)
Nat Rev Immunol. 2015 Oct;15(10):599-614. (PMID: 26403194)
Nature. 2012 May 02;485(7396):109-13. (PMID: 22552098)
Front Immunol. 2014 Sep 02;5:420. (PMID: 25228902)
Sci Rep. 2016 Aug 25;6:31959. (PMID: 27558590)
Am J Transl Res. 2024 May 15;16(5):1643-1659. (PMID: 38883351)
Comput Struct Biotechnol J. 2022 Oct 03;20:5622-5638. (PMID: 36284713)
PLoS Genet. 2014 Jun 19;10(6):e1004368. (PMID: 24945926)
Bioinformatics. 1998;14(4):372-3. (PMID: 9632833)
Annu Rev Biophys. 2015;44:143-66. (PMID: 25747594)
Annu Rev Nutr. 2004;24:433-53. (PMID: 15189127)
Science. 2015 Feb 27;347(6225):1002-6. (PMID: 25569111)
J Pathol. 2013 Jan;229(2):176-85. (PMID: 23096265)
Mol Syst Biol. 2011 Apr 12;7:481. (PMID: 21487400)
Cell Metab. 2012 Jun 6;15(6):813-26. (PMID: 22682222)
Nucleic Acids Res. 2018 Jun 1;46(10):e61. (PMID: 29538776)
Sci Adv. 2023 Jun 9;9(23):eadh8502. (PMID: 37285440)
Mol Biol Evol. 2018 May 1;35(5):1092-1103. (PMID: 29390090)
Proc Natl Acad Sci U S A. 2014 Apr 15;111(15):5670-5. (PMID: 24706797)
EMBO Rep. 2019 Nov 5;20(11):e48220. (PMID: 31482640)
Proc Natl Acad Sci U S A. 2016 Apr 19;113(16):4350-5. (PMID: 27044108)
Methods Mol Biol. 2014;1170:113-44. (PMID: 24906312)
Gene. 2013 Apr 25;519(1):113-9. (PMID: 23376453)
Immunity. 1999 Jul;11(1):103-13. (PMID: 10435583)
J Immunol. 2017 Feb 1;198(3):1006-1014. (PMID: 28115590)
Nature. 2021 Sep;597(7877):561-565. (PMID: 34497418)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Nat Rev Immunol. 2017 Oct;17(10):647-660. (PMID: 28669985)
Nat Struct Mol Biol. 2023 Nov;30(11):1816-1825. (PMID: 37957305)
Cell. 2014 Sep 11;158(6):1281-1292. (PMID: 25215487)
Nat Methods. 2015 Feb;12(2):147-53. (PMID: 25486063)
Annu Rev Pharmacol Toxicol. 1999;39:295-312. (PMID: 10331086)
Trends Immunol. 2023 Dec;44(12):945-953. (PMID: 37919213)
Curr Opin Cell Biol. 1995 Dec;7(6):825-34. (PMID: 8608013)
EMBO J. 2016 Apr 1;35(7):706-23. (PMID: 26896445)
Science. 2015 Mar 6;347(6226):1259038. (PMID: 25745177)
Nat Rev Immunol. 2003 Jan;3(1):23-35. (PMID: 12511873)
Science. 2017 May 5;356(6337):513-519. (PMID: 28473584)
iScience. 2022 Jan 30;25(2):103827. (PMID: 35198887)
Nature. 2017 Jan 26;541(7638):494-499. (PMID: 28077873)
Dev Comp Immunol. 2020 Aug;109:103697. (PMID: 32330465)
Annu Rev Physiol. 2017 Feb 10;79:541-566. (PMID: 27813830)
Nat Commun. 2022 Mar 22;13(1):1536. (PMID: 35318324)
Cell. 2015 Mar 12;160(6):1111-24. (PMID: 25768907)
Trends Biochem Sci. 2019 Sep;44(9):782-794. (PMID: 31003826)
Curr Protoc. 2023 Apr;3(4):e761. (PMID: 37097194)
Nat Commun. 2023 Oct 3;14(1):6166. (PMID: 37789015)
Cell Signal. 2020 Sep;73:109700. (PMID: 32593651)
Genome Biol. 2003;4(5):P3. (PMID: 12734009)
Proc Natl Acad Sci U S A. 2021 Oct 19;118(42):. (PMID: 34642250)
EMBO J. 2022 Sep 15;41(18):e109353. (PMID: 35920020)
J Biol Chem. 2012 Feb 24;287(9):6208-17. (PMID: 22205705)
Cell Signal. 2014 Feb;26(2):192-7. (PMID: 24219909)
Semin Immunol. 2015 Aug;27(4):286-96. (PMID: 26360589)
J Immunol. 2021 Aug 1;207(3):913-922. (PMID: 34290107)
Immunity. 2008 Oct 17;29(4):565-77. (PMID: 18848473)
Nat Immunol. 2014 Jun;15(6):503-11. (PMID: 24840981)
Nucleic Acids Res. 2018 Apr 6;46(6):2802-2819. (PMID: 29529302)
Nature. 2014 Sep 18;513(7518):440-3. (PMID: 25043031)
Mol Cell. 2019 Mar 7;73(5):959-970.e5. (PMID: 30686592)
Bioinformatics. 2013 Jan 1;29(1):15-21. (PMID: 23104886)
Nat Immunol. 2014 Apr;15(4):323-32. (PMID: 24562310)
Genome Biol. 2020 Feb 27;21(1):44. (PMID: 32102681)
J Immunol. 2008 Mar 15;180(6):4218-26. (PMID: 18322234)
Nat Rev Mol Cell Biol. 2018 Jan;19(1):20-30. (PMID: 29018283)
Cell Death Differ. 2002 Feb;9(2):99-100. (PMID: 11840159)
Nature. 2019 Oct;574(7779):575-580. (PMID: 31645732)
J Mol Evol. 1986;24(1-2):28-38. (PMID: 3104616)
Nucleic Acids Res. 2020 Feb 20;48(3):1029-1042. (PMID: 31504789)
Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):E6117-E6126. (PMID: 28696283)
Genome Res. 2024 Apr 25;34(3):394-409. (PMID: 38508694)
Immunity. 2016 Mar 15;44(3):450-462. (PMID: 26982353)
Genome Biol. 2023 Feb 24;24(1):34. (PMID: 36829202)
Nucleic Acids Res. 2012 Nov 1;40(20):10053-63. (PMID: 22941644)
Nat Immunol. 2015 Aug;16(8):838-849. (PMID: 26147685)
Annu Rev Physiol. 2017 Feb 10;79:567-592. (PMID: 27959619)
Adv Biotechnol (Singap). 2023 Dec 1;1(4):6. (PMID: 39883220)
Mol Cell Proteomics. 2014 Mar;13(3):792-810. (PMID: 24396086)
Curr Opin Immunol. 2014 Feb;26:41-8. (PMID: 24556399)
PLoS Biol. 2006 Jun;4(6):e180. (PMID: 16700628)
J Immunol. 2006 Oct 1;177(7):4907-16. (PMID: 16982933)
Substance Nomenclature:
0 (RNA, Messenger)
0 (Lipopolysaccharides)
0 (5' Untranslated Regions)
0 (Codon)
0 (Cytokines)
0 (Lipopolysaccharides)
0 (5' Untranslated Regions)
0 (Codon)
0 (Cytokines)
Entry Date(s):
Date Created: 20250918 Date Completed: 20250923 Latest Revision: 20250925
Update Code:
20250925
PubMed Central ID:
PMC12456811
DOI:
10.1371/journal.pbio.3003403
PMID:
40966232
Database:
MEDLINE
Weitere Informationen
Macrophages require rapid and tightly controlled regulatory mechanisms to respond to environmental disruptions. While transcriptional regulation has been well characterized, the mechanisms underlying translational control in macrophages remain poorly understood. Here, we investigated the dynamics of mRNA translation in mouse macrophages during acute, intermediate, and prolonged LPS exposure. Our results reveal clear phase-specific translational regulation during macrophage polarization, which initially increases the synthesis of inflammatory mediators and cytokines, while simultaneously suppressing the expression of cell cycle-related genes. Mechanistically, we observed pervasive upstream translation in the 5' UTRs of cell cycle-related mRNAs, which contributes to cell cycle arrest during the early phase of inflammatory response. Notably, we identified a unique codon preference toward A/U in the third position of codons in macrophages, which contrasts with the G/C preference commonly observed in other tissues. AU codon preference increases the stability and translation efficiency of cell cycle-related mRNAs, promoting cell cycle restoration after extended LPS exposure. These findings reveal that uORF translation and codon usage bias are critical components of translational regulation during macrophage polarization, highlighting a potential therapeutic intervention for modulating immune activation via macrophage-specific codon optimization.
(Copyright: © 2025 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
The authors declare that there are no competing interests.