title: Gem depletion: amyotrophic lateral sclerosis and spinal muscular atrophy crossover.
abstract: The determining factor of spinal muscular atrophy (SMA), the most common motor neuron degenerative disease of childhood, is the survival motor neuron (SMN) protein. SMN and its Gemin associates form a complex that is indispensible for the biogenesis of small nuclear ribonucleoproteins (snRNPs), which constitute the building blocks of spliceosomes. It is as yet unclear whether a decreased capacity of SMN in snRNP assembly, and, hence, transcriptome abnormalities, account for the specific neuromuscular phenotype in SMA. Across metazoa, the SMN-Gemins complex concentrates in multiple nuclear gems that frequently neighbour or overlap Cajal bodies. The number of gems has long been known to be a faithful indicator of SMN levels, which are linked to SMA severity. Intriguingly, a flurry of recent studies have revealed that depletion of this nuclear structure is also a signature feature of amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron disease. This review discusses such a surprising crossover in addition to highlighting the most recent work on the intricate world of spliceosome building, which seems to be at the heart of motor neuron physiology and survival.
authors.affiliation: Department of Physiology and Biochemistry, University of Malta, Msida 2080, Malta.
authors.forename: Ruben J
authors.initials: RJ
authors.lastname: Cauchi
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics* / Q000378:metabolism; D055532:SMN Complex Proteins / Q000235:genetics* / Q000378:metabolism; D017381:Spliceosomes / Q000235:genetics / Q000378:metabolism
chemical_list: D017411:Ribonucleoproteins, Small Nuclear; D055532:SMN Complex Proteins
keywords: Amyotrophic lateral sclerosis; Cajal body; Gems; SMN-Gemins complex; Spinal muscular atrophy