Science and Research

RUNX1 interacts with lncRNA SMANTIS to regulate monocytic cell functions

Monocytes, the circulating macrophage precursors, contribute to diseases like atherosclerosis and asthma. Long non-coding RNAs (lncRNAs) have been shown to modulate the phenotype and inflammatory capacity of monocytes. We previously discovered the lncRNA SMANTIS, which contributes to cellular phenotype expression by controlling BRG1 in mesenchymal cells. Here, we report that SMANTIS is particularly highly expressed in monocytes and lost during differentiation into macrophages. Moreover, different types of myeloid leukemia presented specific SMANTIS expression patterns. Interaction studies revealed that SMANTIS binds RUNX1, a transcription factor frequently mutated in AML, primarily through its Alu-element on the RUNT domain. RNA-seq after CRISPR/Cas9-mediated deletion of SMANTIS or RUNX1 revealed an association with cell adhesion and both limited the monocyte adhesion to endothelial cells. Mechanistically, SMANTIS KO reduced RUNX1 genomic binding and altered the interaction of RUNX1 with EP300 and CBFB. Collectively, SMANTIS interacts with RUNX1 and attenuates monocyte adhesion, which might limit monocyte vascular egress.

  • Weiss, L. M.
  • Warwick, T.
  • Zehr, S.
  • Günther, S.
  • Wolf, S.
  • Schmachtel, T.
  • Izquierdo Ponce, J.
  • Pálfi, K.
  • Teichmann, T.
  • Schneider, A.
  • Stötzel, J.
  • Knapp, S.
  • Weigert, A.
  • Savai, R.
  • Rieger, M. A.
  • Oellerich, T.
  • Wittig, I.
  • Oo, J. A.
  • Brandes, R. P.
  • Leisegang, M. S.

Keywords

  • *RNA, Long Noncoding/genetics/metabolism
  • Humans
  • *Monocytes/metabolism
  • *Core Binding Factor Alpha 2 Subunit/metabolism/genetics
  • Cell Adhesion/genetics
  • Cell Differentiation
Publication details
DOI: 10.1038/s42003-024-06794-2
Journal: Commun Biol
Pages: 1131 
Number: 1
Work Type: Original
Location: UGMLC
Disease Area: LC, General Lung and Other
Partner / Member: JLU
Access-Number: 39271940

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