SMN interacts with a novel family of hnRNP and spliceosomal proteins

Spinal muscular atrophy (SMA) is a common neurodegenerative disease caused by deletion or loss-of-function mutations of the survival of motor neurons (SMN) protein. SMN is in a complex with several proteins, including Gemin2, Gemin3 and Gemin4, and it plays important roles in small nuclear ribonucle oprotein (snRNP) biogenesis and in pre-mRNA splicing. Here, we characterize three new hnRNP proteins, collectively referred to as hnRNP Qs, which are derived from alternative splicing of a single gene. The hnRNP Q proteins in teract with SMN, and the most common SMN mutant found in SMA patients is de fective in its interactions with them. We further demonstrate that hnRNP Qs are required for efficient pre-mRNA splicing in vitro. The hnRNP Q protein s may provide a molecular link between the SMN complex and splicing.