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 ribonucleoprotein (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 interact with SMN, and the most common SMN mutant found in SMA patients is defective in its interactions with them. We further demonstrate that hnRNP Qs are required for efficient pre-mRNA splicing in vitro. The hnRNP Q proteins may provide a molecular link between the SMN complex and splicing.
Mourelatos
Z
Z
Howard Hughes Medical Institute and Department of Biochemistry & Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6148, USA.
Abel
L
L
Yong
J
J
Kataoka
N
N
Dreyfuss
G
G
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D017362:Cyclic AMP Response Element-Binding Protein; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D012326:RNA Splicing; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins / Q000378:metabolism*; D055532:SMN Complex Proteins; D017381:Spliceosomes / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D017362:Cyclic AMP Response Element-Binding Protein; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D055532:SMN Complex Proteins