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Abstract:
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.
The long non-coding RNA SMANTIS interacts with the transcription factor
RUNX1 in an Alu-RUNT-dependent manner in monocytes and limits monocyte
adhesion to endothelial cells.
