| First Author | Donlin-Asp PG | Year | 2017 |
| Journal | Cell Rep | Volume | 18 |
| Issue | 7 | Pages | 1660-1673 |
| PubMed ID | 28199839 | Mgi Jnum | J:355096 |
| Mgi Id | MGI:7737777 | Doi | 10.1016/j.celrep.2017.01.059 |
| Citation | Donlin-Asp PG, et al. (2017) The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly. Cell Rep 18(7):1660-1673 |
| abstractText | Spinal muscular atrophy (SMA) is a motor neuron disease caused by reduced levels of the survival of motor neuron (SMN) protein. SMN is part of a multiprotein complex that facilitates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). SMN has also been found to associate with mRNA-binding proteins, but the nature of this association was unknown. Here, we have employed a combination of biochemical and advanced imaging methods to demonstrate that SMN promotes the molecular interaction between IMP1 protein and the 3' UTR zipcode region of beta-actin mRNA, leading to assembly of messenger ribonucleoprotein (mRNP) complexes that associate with the cytoskeleton to facilitate trafficking. We have identified defects in mRNP assembly in cells and tissues from SMA disease models and patients that depend on the SMN Tudor domain and explain the observed deficiency in mRNA localization and local translation, providing insight into SMA pathogenesis as a ribonucleoprotein (RNP)-assembly disorder. |
