HMGB1 prefers to interact with structural RNAs and regulates rRNA methylation modification and translation in HeLa cells

• Published in: BMC genomics Vol. 25; no. 1; p. 345
• Main Authors: Liao, Meimei, Cao, Jiarui, Chen, Wen, Wang, Mengwei, Jin, Zhihui, Ye, Jia, Ren, Yijun, Wei, Yaxun, Xue, Yaqiang, Chen, Dong, Zhang, Yi, Chen, Sen
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 05-04-2024; BioMed Central; BMC
• Subjects: 28S rRNA; Analysis; Apoptosis; Autoimmunity; Axon guidance; Binding sites; Biogenesis; Biosynthesis; Cancer; Cell differentiation; Cell growth; Cellular signal transduction; Chromosomal proteins; Crosslinking; Cytokines; Differentiation (biology); DNA; DNA methylation; Extracellular matrix; Gene expression; Gene regulation; Genes; Genetic aspects; Genetic research; Genetic transcription; Genetic translation; Genomes; HeLa Cells; Hepatitis C; HMGB1; HMGB1 protein; HMGB1 Protein - genetics; HMGB1 Protein - metabolism; Humans; Immunoprecipitation; Inflammation; iRIP-seq; Ischemia; Localization; Messenger RNA; Methylation; Methylation modification; Nucleic acids; Osteoclastogenesis; Physiological aspects; Protein biosynthesis; Protein synthesis; Proteins; Proteomics; Reperfusion; Ribonucleic acid; Ribosomes; RNA; RNA modification; RNA polymerase; RNA, Ribosomal, 28S - metabolism; RNA, Small Nucleolar - chemistry; RNA, Small Nucleolar - genetics; RNA, Small Nucleolar - metabolism; rRNA 28S; Signal transduction; snoRNAs; Software; Structured RNA; Transcription; Transcription factors; China; Translation; snoRNAs; 28S rRNA; Cancer cells; Structured RNA; HMGB1; iRIP-seq; Methylation modification
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-024-10204-6

High-mobility group B1 (HMGB1) is both a DNA binding nuclear factor modulating transcription and a crucial cytokine that mediates the response to both infectious and noninfectious inflammation such as autoimmunity, cancer, trauma, and ischemia reperfusion injury. HMGB1 has been proposed to control ribosome biogenesis, similar as the other members of a class of HMGB proteins.
Here, we report that HMGB1 selectively promotes transcription of genes involved in the regulation of transcription, osteoclast differentiation and apoptotic process. Improved RNA immunoprecipitation by UV cross-linking and deep sequencing (iRIP-seq) experiment revealed that HMGB1 selectively bound to mRNAs functioning not only in signal transduction and gene expression, but also in axon guidance, focal adhesion, and extracellular matrix organization. Importantly, HMGB1-bound reads were strongly enriched in specific structured RNAs, including the domain II of 28S rRNA, H/ACA box snoRNAs including snoRNA63 and scaRNAs. RTL-P experiment showed that overexpression of HMGB1 led to a decreased methylation modification of 28S rRNA at position Am2388, Cm2409, and Gm2411. We further showed that HMGB1 overexpression increased ribosome RNA expression levels and enhanced protein synthesis.
Taken together, our results support a model in which HMGB1 binds to multiple RNA species in human cancer cells, which could at least partially contribute to HMGB1-modulated rRNA modification, protein synthesis function of ribosomes, and differential gene expression including rRNA genes. These findings provide additional mechanistic clues to HMGB1 functions in cancers and cell differentiation.