Biogenesis of lysosome-related organelles complex 1 subunit 1 pre-mRNA (BLOC1S1 pre-mRNA)

Human BLOC1S1 pre-mRNA is the precursor transcript for the Biogenesis of Lysosome-related Organelles Complex 1 Subunit 1 (BLOC1S1), also known as GCN5L1 (UniProt P78537). The encoded protein is a multifunctional component of the BLOC-1 and BORC complexes, which are essential for the biogenesis, positioning, and trafficking of lysosomes and related organelles (GeneCards). Additionally, BLOC1S1 acts as a mitochondrial protein acetyltransferase, playing a key role in regulating energy metabolism and mitochondrial respiration (UniProt P78537). This pre-mRNA has emerged as a significant therapeutic target in neurodegenerative diseases, particularly Amyotrophic Lateral Sclerosis (ALS), where BLOC1S1 is pathologically upregulated (Mol Ther, 2026). Experimental therapeutic strategies utilize splice-switching antisense oligonucleotides (SSOs) to target the pre-mRNA, inducing nonsense-mediated decay or exon skipping to reduce protein levels and restore cellular homeostasis (Mol Ther, 2026). The mature BLOC1S1 mRNA is also a well-known substrate for Regulated IRE1-Dependent Decay (RIDD), a process mediated by the ER stress sensor IRE1 alpha (Bright et al., 2015). Consequently, BLOC1S1 expression levels serve as a critical biomarker for monitoring IRE1 activity and endoplasmic reticulum stress in conditions such as cancer and metabolic disorders (NIH). Mutations in the BLOC1S1 gene are linked to rare genetic disorders like leukodystrophy and share pathways with Hermansky-Pudlak syndrome (NIH). Targeting the pre-mRNA offers a precision medicine approach to modulate mitochondrial and lysosomal functions in various disease contexts.

Other names

BLOS1 pre-mRNAGCN5L1 pre-mRNABORCS1 pre-mRNART14 pre-mRNAMICoA pre-mRNABiogenesis of lysosomal organelles complex 1 subunit 1 pre-mRNA

Splice-switching to induce nonsense-mediated decay (NMD) or exon skipping to reduce protein expression