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Updated: Jun 13, 2025
09:16
Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
Published on: September 1, 2019
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RUNX1 interacts with lncRNA SMANTIS to regulate monocytic cell functions.
Lisa M Weiss1,2, Timothy Warwick1,2, Simonida Zehr1,2
1Goethe University Frankfurt, Institute for Cardiovascular Physiology, Frankfurt, Germany.
Communications Biology
|September 13, 2024
Summary
The long non-coding RNA SMANTIS regulates monocyte adhesion by interacting with RUNX1. This interaction may limit monocyte movement into tissues, impacting inflammatory diseases.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- Monocytes are crucial precursors to macrophages involved in inflammatory diseases.
- Long non-coding RNAs (lncRNAs) regulate monocyte function and inflammation.
- SMANTIS, a previously identified lncRNA, influences cellular phenotype.
Purpose of the Study:
- To investigate the role of SMANTIS in monocytes and its mechanism of action.
- To explore SMANTIS expression patterns in myeloid leukemias.
- To elucidate the interaction between SMANTIS and RUNX1 in monocyte adhesion.
Main Methods:
- Quantification of SMANTIS expression in monocytes and during differentiation.
- Analysis of SMANTIS expression in myeloid leukemia subtypes.
- RNA sequencing following CRISPR/Cas9-mediated deletion of SMANTIS or RUNX1.
- Co-immunoprecipitation and chromatin immunoprecipitation assays to study protein-RNA and protein-DNA interactions.
Main Results:
- SMANTIS is highly expressed in monocytes and downregulated during macrophage differentiation.
- Distinct SMANTIS expression profiles were observed in different myeloid leukemias.
- SMANTIS binds to the transcription factor RUNX1, influencing its genomic binding and interactions with EP300 and CBFB.
- Deletion of SMANTIS or RUNX1 impairs monocyte adhesion to endothelial cells.
Conclusions:
- SMANTIS plays a significant role in regulating monocyte adhesion to endothelial cells.
- The SMANTIS-RUNX1 interaction attenuates monocyte adhesion, potentially limiting vascular egress.
- SMANTIS represents a potential therapeutic target for inflammatory conditions involving monocyte recruitment.
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