An alternative cytoplasmic SFPQ isoform with reduced phase separation potential is up-regulated in ALS.

ABSTRACT: Splicing factor proline- and glutamine-rich (SFPQ) is an RNA binding protein that broadly regulates RNA metabolism. Although its nuclear roles are well studied, evidence of SFPQ's cytoplasmic functionality is emerging. Altered expression and nuclear-to-cytoplasmic redistribution of SFPQ have been recognized in amyotrophic lateral sclerosis (ALS) pathology, yet the mechanistic bases for these phenomena remain undetermined. We identified altered SFPQ splicing in ALS, increasing the expression of an alternative mRNA isoform lacking a nuclear localization sequence, which we termed "altSFPQ." We find that altSFPQ mRNA contributes to SFPQ autoregulation and is highly unstable yet exhibits context-specific translation with cytoplasm-predominant localization. Notably, reduced canonical SFPQ coinci

SUBMITTER: Neeves J 

PROVIDER: S-EPMC12372870 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature