Dbr1-flox Mouse

Dbr1, short for RNA DEBRANCHING ENZYME 1, is a rate-limiting enzyme in the lariat intronic RNA (lariRNA) decay process. During pre-mRNA splicing, introns are removed as branched lariat RNAs, and Dbr1 debranches them in the rate-limiting step of lariat turnover. This process is crucial for intron recycling and likely regulates the production of translation-competent mRNAs [2,3,5].

In plant studies, sequestration of Dbr1 into stress granules (SGs) by SICKLE (SIC) enhances lariRNA accumulation, which promotes the transcription of heat-stress tolerance genes, highlighting its role in plant heat-stress responses [1]. In human cells, Dbr1 depletion leads to a 20-fold increase in lariats and increased exon skipping, indicating its role in proper splicing and spliceosome recycling [3,5]. Inherited DBR1 deficiency in humans is associated with brainstem viral encephalitis, as DBR1-deficient cells have impaired stress granule assembly, which in turn impairs PKR-mediated antiviral immunity [4,6]. A founder DBR1 variant also causes a lethal form of congenital ichthyosis [7]. In esophageal squamous cell carcinoma, lower DBR1 expression is associated with a worse prognosis [8].

In summary, Dbr1 is essential for lariat intronic RNA decay, which impacts mRNA processing, intron turnover, and splicing. Studies on Dbr1-related genetic models, such as human DBR1-deficient cases, have revealed its importance in various biological processes and disease conditions, including plant heat-stress tolerance, viral encephalitis, congenital ichthyosis, and esophageal squamous cell carcinoma prognosis.