Biogenesis of lysosome-related organelles complex 1 subunit 1 (Bloc1s1) pre-mRNA (Bloc1s1 pre-mRNA)

Mouse Bloc1s1 pre-mRNA is a precursor messenger RNA encoding the Biogenesis of lysosome-related organelles complex 1 subunit 1 protein. It is widely recognized as a primary and highly conserved substrate for the endoribonuclease activity of Inositol-requiring enzyme 1 alpha (IRE1α), a key sensor of the unfolded protein response (UPR) located in the endoplasmic reticulum [PMID: 19710424]. Under conditions of endoplasmic reticulum (ER) stress, activated IRE1α cleaves Bloc1s1 pre-mRNA at a specific consensus site, leading to its rapid degradation through a pathway termed Regulated IRE1-dependent decay (RIDD) [PMID: 25692214]. This degradation results in the depletion of the BLOS1 protein, which normally functions within the BLOC-1 complex to facilitate lysosome biogenesis and endosomal trafficking [PMID: 22253405]. Because of its high sensitivity and specificity to IRE1α RNase activity, Bloc1s1 mRNA levels are frequently used as a robust biomarker for monitoring ER stress and the efficacy of IRE1α-targeted therapies [PMID: 31112131]. While not a traditional therapeutic target itself, the modulation of Bloc1s1 levels via IRE1α is relevant in the context of metabolic diseases such as non-alcoholic steatohepatitis (NASH) and various cancers where the UPR is chronically activated [PMID: 30531974]. Experimental approaches using antisense oligonucleotides have targeted Bloc1s1 to study its role in lipid metabolism and lysosomal positioning [PMID: 30108118]. Overall, Bloc1s1 pre-mRNA serves as a critical link between ER stress sensing and the regulation of cellular organelle dynamics.

Other names

Blos1 pre-mRNAGblp pre-mRNArt14 pre-mRNABiogenesis of lysosome-related organelles complex 1 subunit 1

Substrate for IRE1α-mediated endonucleolytic cleavage during the unfolded protein response.