Elizabeth T. Bartom

Abstract La-related protein 1 (LARP1) is an RNA-binding protein and downstream effector of mTOR and CDK9 signaling that regulates translation of mRNAs containing a 5’-terminal oligopyrimidine motif. While elevated LARP1 expression has been linked to poor prognosis in acute myeloid leukemia (AML), its mechanistic role remains unclear. Using CRISPR/Cas9-mediated LARP1 knockout and multi-omics analyses, we investigated LARP1’s role in AML.

ACAT2 Acyl-CoA: cholesterol acyltransferase 2 ACLY ATP citrate lyase ADP adenosine diphosphate AI aromatase inhibitor AKT protein kinase B AMP adenosine monophosphate BC breast cancer BCL2 B cell lymphoma 2 CLS crown-like structures CYP19A1 cytochrome P450 family 19 subfamily A member 1 CYP1B1 cytochrome P450 family 1 subfamily B member 1 ECM extracellular matrix EGFR epidermal growth factor receptor ER estrogen receptor FASN fatty acid synthase FBA flux-based analysis GLS generalized least...

Abstract CRISPR-based transcriptional activation (CRISPRa) has extensive research and clinical potential. Here, we show that commonly used CRISPRa systems can exhibit pronounced cytotoxicity. We demonstrate the toxicity of CRISPRa vectors expressing the activation domains (ADs) of the transcription factors p65 and HSF1, components of the synergistic activation mediator (SAM) CRISPRa system.