title: Chaperoning ribonucleoprotein biogenesis in health and disease.
abstract: The survival motor neuron (SMN) protein is part of a macromolecular complex that functions in the biogenesis of small nuclear ribonucleoproteins (snRNPs)--the essential components of the pre-messenger RNA splicing machinery--as well as probably other RNPs. Reduced levels of SMN expression cause the inherited motor neuron disease spinal muscular atrophy (SMA). Knowledge of the composition, interactions and functions of the SMN complex has advanced greatly in recent years. The emerging picture is that the SMN complex acts as a macromolecular chaperone of RNPs to increase the efficiency and fidelity of RNA-protein interactions in vivo, and to provide an opportunity for these interactions to be regulated. In addition, it seems that RNA metabolism deficiencies underlie SMA. Here, a dual dysfunction hypothesis is presented in which two mechanistically and temporally distinct defects--that are dependent on the extent of SMN reduction in SMA--affect the homeostasis of specific messenger RNAs encoding proteins essential for motor neuron development and function.
authors.affiliation: Dulbecco Telethon Institute, Institute of Cell Biology (CNR), Via E. Ramarini 32, 00016 Monterotondo Scalo, Rome, Italy. livio.pellizzoni@ibc.cnr.it
authors.forename: Livio
authors.initials: L
authors.lastname: Pellizzoni
mesh_terms: D000818:Animals; D002470:Cell Survival; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D006262:Health; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology*; D009134:Muscular Atrophy, Spinal / Q000209:etiology* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism*; D055532:SMN Complex Proteins
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins