Highlights
- •A global N6-methyladenosine (m6A) RNA modification pattern in Tp-infected macrophages was systematically dissected.
- •Aberrant genes with m6A-modification from these macrophages were enriched in infection-related pathways.
- •RNA-seq revealed function confusion of Tp-infected macrophage, which, together with MeRIP, displayed particular patterns.
Abstract
Background
Treponema pallidum (Tp) is a widespread and destructive pathogen that leads to syphilis. As the acknowledged
executor of host immunity, macrophage plays vital roles in combating the invasion
and migration of Tp. However, the mechanisms of these processes are largely unknown, especially the critical
driver genes and associated modifications.
Objective
We aimed to systematically dissect the global N6-methyladenosine (m6A) RNA modification patterns in Tp-infected macrophages.
Methods
The RNA of Tp-infected/non-infected macrophage was extracted, followed by mRNA sequencing and methylated
RNA immunoprecipitation (MeRIP) sequencing. Bioinformatics analysis was executed by
m6A peaks and motifs identification, Gene ontology and signaling pathways analysis of
differentially expressed genes, and comprehensive comparison. The m6A levels were measured by RNA Methylation Assay, and m6A modified genes were determined by qPCR.
Results
Totally, 2623 unique and 3509 common m6A peaks were proved along with related transcripts in Tp-infected macrophages. The common m6A-related genes were enriched in the signals of oxidative stress, cell differentiation,
and angiogenesis, while unique genes in those of metabolism, inflammation, and infection.
And differentially expressed transcripts revealed various biological processes and
pathways associated with catabolic and infection. They also experienced comprehensive
analysis due to hyper-/hypo-methylation. And the m6A level of macrophage was elevated, along with qPCR validation of specific genes.
Conclusion
With a particular m6A transcriptome-wide map, our study provides unprecedented insights into the RNA modification
of macrophage stimulated by Tp in vitro, which partially differs from other infections and may provide clues to
explore the immune process for syphilis.
Key words
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Article info
Publication history
Published online: February 18, 2023
Accepted:
February 16,
2023
Received in revised form:
December 18,
2022
Received:
June 26,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
