tRNA queuosine modification enzyme modulates the growth and microbiome recruitment to breast tumors

Zhang, Jilei; Liu, Rong; Zhang, Yongguo; Matuszek, Żaneta; Xia, Yinglin; Pan, Tao; Sun, Jun

doi:10.21203/rs.2.21087/v1

Cited by 14 publications

(18 citation statements)

References 47 publications

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“… 35 In our recent study, we found Butyrivibrio fibrisolvens -related clones, which belong to the Firmicutes phylum, in breast tumors with a xenograft mouse model. 36 …”

Section: Breast Microbiome and Breast Diseasesmentioning

confidence: 99%

“…For example, the systemic counter-interactions between microbes and immune items of IL-6 and neutrophils have been indicated in breast cancer. 36 , 72 It is known that both neutrophils and lymphocytes are modulated by the microbiota and inflammation. The neutrophil-associated immune responses to the GI microbiome significantly impact carcinogenesis progress in non-intestinal tissues, such as mammary glands.…”

Section: Gut Microbiome and Breast Cancermentioning

confidence: 99%

“…Intestinal bacteria including Lachnospiraceae , Lactobacillus and Alistipes were found to be markedly altered in xenograft nude mice after challenging breast cancer cells. 36 …”

Section: Gut Microbiome and Breast Cancermentioning

confidence: 99%

“…We found evidence that microbiome was involved in the growth of breast cancer in vivo . 36 The correlation of the gut microbiome and breast cancer is expected to aid future diagnostic assays for clinical application. For instance, metabolites (estrogen metabolites) combined with bacteria l biomarkers (Bacteroidetes-to-Firmicutes ratio) might be a new diagnosis method for breast cancer.…”

Section: Gut Microbiome and Breast Cancermentioning

confidence: 99%

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Breast and gut microbiome in health and cancer

2021

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The microbiota plays essential roles in health and disease, in both the intestine and the extra-intestine. Dysbiosis of the gut microbiota causes dysfunction in the intestine, which leads to inflammatory, immune, and infectious diseases. Dysbiosis is also associated with diseases beyond the intestine via microbial translocation or metabolisms. The in situ breast microbiome, which may be sourced from the gut through lactation and sexual contact, could be altered and cause breast diseases. In this review, we summarize the recent progress in understanding the interactions among the gut microbiome, breast microbiome, and breast diseases. We discuss the intestinal microbiota, microbial metabolites, and roles of microbiota in immune system. We emphasize the novel roles and mechanisms of the microbiome (both in situ and gastrointestinal sourced) and bacterial products in the development and progression of breast cancer. The intestinal microbial translocation suggests that the gut microbiome is translocated to the skin and subsequently to the breast tissue. The gut bacterial translocation is also due to the increased intestinal permeability. The breast and intestinal microbiota are important factors in maintaining healthy breasts. Micronutrition queuine (Q) is derived from a de novo synthesized metabolite in bacteria. All human cells use queuine and incorporate it into the wobble anticodon position of specific transfer RNAs. We have demonstrated that Q modification regulates genes critical in tight junctions and migration in human breast cancer cells and a breast tumor model. We further discuss the challenges and future perspectives that can move the field forward for prevention, diagnosis, and treatment of breast diseases.

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“… 35 In our recent study, we found Butyrivibrio fibrisolvens -related clones, which belong to the Firmicutes phylum, in breast tumors with a xenograft mouse model. 36 …”

Section: Breast Microbiome and Breast Diseasesmentioning

confidence: 99%

Section: Gut Microbiome and Breast Cancermentioning

confidence: 99%

“…Intestinal bacteria including Lachnospiraceae , Lactobacillus and Alistipes were found to be markedly altered in xenograft nude mice after challenging breast cancer cells. 36 …”

Section: Gut Microbiome and Breast Cancermentioning

confidence: 99%

Section: Gut Microbiome and Breast Cancermentioning

confidence: 99%

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Breast and gut microbiome in health and cancer

2021

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“…However, they are important metabolites that speci cally modify certain human tRNAs to promote protein folding 9,45,46 . The speci c role that these metabolites play in humans remains under investigation, though there is at least some evidence that they may also have anti-cancer activity in addition to their regulatory roles in commensal bacteria 47,48 . Here, we demonstrate that PreQ1 also has speci c interactions with important regulatory human RNAs, including TERC, HIST1H3F, and HIST2H2BF, all of which have been shown previously to form stable RNA structures.…”

Section: Resultsmentioning

confidence: 99%

A Chemical Probe Based on the PreQ1 Metabolite Enables Transcriptome-wide Mapping of Binding Sites

Balaratnam¹,

Rhodes²,

Bume³

et al. 2021

Preprint

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The role of metabolite-responsive riboswitches in regulating gene expression in bacteria is well known and makes them useful systems for the study of RNA-small molecule interactions. Here, we study the PreQ1 riboswitch system, assessing sixteen diverse PreQ1-derived probes for their ability to selectively modify the riboswitch aptamer covalently. For the most active probe, a diazirine-based photocrosslinker, X-ray crystallography and gel-based competition assays demonstrated the mode of binding of the ligand to the aptamer, and functional assays demonstrated that the probe retains activity against the full riboswitch. Transcriptome-wide mapping using Chem-CLIP revealed a highly selective interaction between the bacterial aptamer and the small molecule. In addition, a small number of RNA targets in endogenous human transcripts were found to bind specifically to PreQ1, providing evidence for candidate PreQ1 aptamers in human RNA. This work demonstrates a stark influence of linker chemistry and structure on the ability of molecules to crosslink RNA, reveals that the PreQ1 aptamer/ligand pair are broadly useful for chemical biology applications, and provides insights into how PreQ1 interacts with human RNAs.

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Functional integration of a semi-synthetic azido-queuosine derivative into translation and a tRNA modification circuit

Bessler

Kaur

Vogt

et al. 2022

Nucleic Acids Research

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Substitution of the queuine nucleobase precursor preQ1 by an azide-containing derivative (azido-propyl-preQ1) led to incorporation of this clickable chemical entity into tRNA via transglycosylation in vitro as well as in vivo in Escherichia coli, Schizosaccharomyces pombe and human cells. The resulting semi-synthetic RNA modification, here termed Q-L1, was present in tRNAs on actively translating ribosomes, indicating functional integration into aminoacylation and recruitment to the ribosome. The azide moiety of Q-L1 facilitates analytics via click conjugation of a fluorescent dye, or of biotin for affinity purification. Combining the latter with RNAseq showed that TGT maintained its native tRNA substrate specificity in S. pombe cells. The semi-synthetic tRNA modification Q-L1 was also functional in tRNA maturation, in effectively replacing the natural queuosine in its stimulation of further modification of tRNAAsp with 5-methylcytosine at position 38 by the tRNA methyltransferase Dnmt2 in S. pombe. This is the first demonstrated in vivo integration of a synthetic moiety into an RNA modification circuit, where one RNA modification stimulates another. In summary, the scarcity of queuosinylation sites in cellular RNA, makes our synthetic q/Q system a ‘minimally invasive’ system for placement of a non-natural, clickable nucleobase within the total cellular RNA.

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tRNA queuosine modification enzyme modulates the growth and microbiome recruitment to breast tumors

Cited by 14 publications

References 47 publications

Breast and gut microbiome in health and cancer

Breast and gut microbiome in health and cancer

A Chemical Probe Based on the PreQ1 Metabolite Enables Transcriptome-wide Mapping of Binding Sites

Functional integration of a semi-synthetic azido-queuosine derivative into translation and a tRNA modification circuit

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