SLM-2 CRISPR Activation Plasmid (h): sc-407141-ACT

Human KHDRBS3 encodes SLM-2, a STAR family RNA-binding protein that regulates alternative splicing and RNA processing through recognition of specific sequence motifs in pre-mRNAs. SLM-2 influences transcript isoform selection in a tissue- and context-dependent manner, shaping programs linked to neuronal function and broader post-transcriptional gene regulation. By modulating splice-site choice and mRNA maturation, KHDRBS3 can affect signaling outputs and proteome diversity, making it relevant for studying RNA regulatory networks and dysregulated splicing observed across complex diseases. Altered expression or splicing-factor imbalance involving SLM-2 has been investigated in mechanisms of transcriptional coupling to RNA processing and disease-associated isoform switching.

SLM-2 CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous KHDRBS3 expression without altering the underlying DNA sequence.

SLM-2 CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the KHDRBS3 locus in human cell lines. The system is built around a catalytically inactive Cas9 (dCas9) carrying two inactivating mutations (D10A and N863A) that eliminate nuclease activity while preserving DNA binding. This dCas9 is fused to VP64, a potent transcriptional activator, and is co-expressed with a blasticidin resistance gene for selection. The second plasmid encodes the MS2-p65-HSF1 fusion protein, a secondary activator complex that works in concert with dCas9-VP64, alongside a hygromycin resistance gene. The third plasmid encodes a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers that recruit the MS2-p65-HSF1 complex to the activation site, accompanied by a puromycin resistance gene. The three plasmids are delivered at a 1:1:1 mass ratio for balanced expression of all system components.

Once assembled at the target locus, the SAM complex binds within approximately 200 bp upstream of the KHDRBS3 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous SLM-2 expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native KHDRBS3 locus and enabling the study of SLM-2-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of SLM-2 pathway restoration in tumor cells with silenced or reduced KHDRBS3 expression.

For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.