RNA lariat debranching enzyme (DBR1)

**RNA lariat debranching enzyme (DBR1)** is a highly conserved **metal-dependent phosphoesterase** responsible for selective hydrolysis of the unique 2′–5′ phosphodiester bond at the branchpoint of intron lariat RNAs, which are produced as byproducts of pre-mRNA splicing[1][2][3][4][5]. DBR1 is the **sole enzyme** in higher eukaryotes that catalyzes this debranching reaction, driving turnover of lariats into linear introns for subsequent degradation or processing into noncoding RNAs such as snoRNAs and certain miRNAs[2][3][4]. Functionally, DBR1 activity is essential for proper spliceosome recycling and efficient gene expression, with its loss leading to the nuclear accumulation of lariat RNAs, delayed recycling, and increased exon skipping[1]. Human DBR1 localizes mainly to the nucleus, possesses a conserved N-terminal catalytic domain that requires iron for activity, and features a flexible C-terminal domain implicated in stability and protein-protein interactions[4]. Dysregulation or genetic deficiency in DBR1 has been linked to a variety of diseases, including cancer, viral infections (especially HIV-1), neurodegenerative diseases like ALS, and immunoglobulin class switch recombination errors, underscoring its central role in RNA metabolism and cellular homeostasis[4]. No approved pharmaceuticals target DBR1, but it is an active area of therapeutic investigation, particularly for disorders involving aberrant RNA processing and retroelement pathology[3][4].

Other names

Lariat debranching enzymeXGIPlariat debranching enzymeRNA lariat debranching enzymedebranching enzyme homolog 1

Enzyme inhibition (prospective drugs aim to inhibit the 2’,5’-phosphodiesterase activity to stabilize lariats or reduce retroelement activity)[3].