Biochemistry and biophysics reports · 2026
Epitranscriptomic profiling of VSMC phenotypes reveals uridine modifications linked to post-transcriptional regulation.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Reinberger Tobias, Ismail Ayat, Falk Torben, Fuß Janina, Wiechert Anja, Hammer Elke, Zeller Tanja, Wohlers Inken
Аннотация
BACKGROUND: The phenotypic plasticity of vascular smooth muscle cells (VSMCs) can modulate atherosclerosis progression. Although several gene regulatory steps towards pro-inflammatory phenotypes have been well-studied, epitranscriptomic changes during this transition and their regulatory roles remain unexplored.
METHODS AND RESULTS: Primary human VSMCs were stimulated with TGF-β1 to induce a contractile, matrix-producing state and with IL-1β plus PDGF-BB to induce a highly energetic, pro-inflammatory state, confirmed by Illumina bulk RNA sequencing and proteomics. Untargeted screening of mRNA base modifications using Oxford Nanopore Technologies direct RNA sequencing and xPore analysis revealed differential uridine modification within a GUUUU motif in pro-inflammatory VSMCs. Modified uridines were enriched in 3'-UTRs and at predicted RNA structural contexts consistent with accessibility, with implications for poly(A) tail dynamics and miRNA binding.
CONCLUSIONS: Both TGF-β1 and PDGF-BB/IL-1β induce distinct epitranscriptomic landscapes composed of different modification types, often co-localized in the same transcript. Differentially modified uridines in mRNAs are abundant in a high-energy, pro-inflammatory VSMC state and are associated with post-transcriptional regulation. In summary, these findings suggest that U-centered nanopore signal changes are associated with post-transcriptional regulatory features during VSMC phenotypic transitions.
METHODS AND RESULTS: Primary human VSMCs were stimulated with TGF-β1 to induce a contractile, matrix-producing state and with IL-1β plus PDGF-BB to induce a highly energetic, pro-inflammatory state, confirmed by Illumina bulk RNA sequencing and proteomics. Untargeted screening of mRNA base modifications using Oxford Nanopore Technologies direct RNA sequencing and xPore analysis revealed differential uridine modification within a GUUUU motif in pro-inflammatory VSMCs. Modified uridines were enriched in 3'-UTRs and at predicted RNA structural contexts consistent with accessibility, with implications for poly(A) tail dynamics and miRNA binding.
CONCLUSIONS: Both TGF-β1 and PDGF-BB/IL-1β induce distinct epitranscriptomic landscapes composed of different modification types, often co-localized in the same transcript. Differentially modified uridines in mRNAs are abundant in a high-energy, pro-inflammatory VSMC state and are associated with post-transcriptional regulation. In summary, these findings suggest that U-centered nanopore signal changes are associated with post-transcriptional regulatory features during VSMC phenotypic transitions.