CHD2-adjacent suppressive regulatory RNA (CHASERR) (CHASERR)

CHASERR (CHD2-adjacent suppressive regulatory RNA) is a highly conserved long non-coding RNA (lncRNA) located immediately upstream of the CHD2 gene on chromosome 15 [1.1.1, 1.3.1]. Its primary biological role is to act as a cis-acting repressor of CHD2, a chromatin remodeler that is critical for normal brain development and neuronal function [1.3.1, 1.5.1]. By maintaining a suppressive traffic jam on the CHD2 promoter, CHASERR ensures that CHD2 protein levels remain within a narrow physiological range [1.1.3]. Haploinsufficiency of CHD2 is a known cause of epilepsy and intellectual disability, making CHASERR an attractive therapeutic target for upregulation strategies [1.2.1, 1.3.1]. Experimental approaches using antisense oligonucleotides (ASOs) to inhibit CHASERR have successfully increased CHD2 expression in preclinical models, offering a potential treatment for CHD2-related disorders [1.2.1, 1.5.4]. However, clinical evidence has recently identified that deletions of CHASERR itself lead to CHD2 overexpression, resulting in a severe, distinct neurodevelopmental syndrome characterized by encephalopathy and cerebral hypomyelination [1.3.2, 1.5.1]. This bidirectional dosage sensitivity, often called the Goldilocks problem, necessitates precise titration of any CHASERR-targeting therapy to avoid toxicity [1.4.2, 1.5.4]. Beyond its interaction with CHD2, CHASERR functions as a regulatory hub that scaffolds other non-coding RNAs and has been implicated in the progression of certain cancers like glioma [1.4.1, 1.4.3].

Other names

CHD2-adjacent suppressive regulatory RNALINC01578Long intergenic non-protein coding RNA 15781810026B05RikLnc-CHD2-19NEDFSAB

CHASERR is targeted primarily through antisense oligonucleotides (ASOs) or Gapmers that induce its degradation or interfere with its regulatory motifs. This inhibition releases the cis-acting repression of the adjacent CHD2 gene, thereby increasing CHD2 mRNA and protein levels to compensate for haploinsufficiency [1.2.1, 1.3.1]. Additionally, certain ASOs can induce the formation of a CHASERR-CHD2 fusion transcript that is exported to the cytoplasm and translated into functional CHD2 protein [1.2.1].