title: [Pre-mRNA splicing: when the spliceosome loses ground].
abstract: Pre-mRNA splicing is an obligatory step required to assemble the vast majority of mRNAs in eukaryotes. In humans, each gene gives rise to at least two transcripts, with an average 6-8 spliced transcripts per gene. Pre-mRNA splicing is not unequivocal. Variations may occur, such that splicing can become alternative, thereby participating in increasing protein variability and restricting the gap that exists between the relatively low number of genes - between 20,000 and 25,000 in humans - and the much higher number of distinct proteins - at least 100,000. In addition, although alternative pre-mRNA splicing often fulfils cell-specific needs, many aberrant splicing events can happen and lead to either hereditary or acquired diseases such as neurodegenerative diseases or cancers. In those cases, alternative splicing events may serve as disease-associated markers, or even as targets for corrective approaches. In this review, we will summarize the main aspects of regulated alternative splicing. We will present the spliceosome, a large ribonucleoprotein complex that orchestrates the splicing reactions and that was recently identified as a preferential target for mutations in several pathologies. We shall discuss some spliceosome-associated defects linked to either cis (i.e on the DNA) or trans (e.g. in proteins) alterations of splicing machinery, like those that have been reported in genetic or acquired diseases.
authors.affiliation: Centre de Regulació Genòmica (CRG), the Barcelona Institute of Science and Technology, Barcelone, Espagne.
authors.forename: Gwendal
authors.initials: G
authors.lastname: Dujardin
authors.affiliation: Centre de Regulació Genòmica (CRG), the Barcelona Institute of Science and Technology, Barcelone, Espagne.
authors.forename: Élisabeth
authors.initials: É
authors.lastname: Daguenet
authors.affiliation: Inserm U1078-ECLA, Université de Bretagne Occidentale, Institut Brestois en Santé Agro Matière (IBSAM), Faculté de médecine, 22, avenue Camille Desmoulins, 29200 Brest, France.
authors.forename: Delphine G
authors.initials: DG
authors.lastname: Bernard
authors.affiliation: Inserm U1078-ECLA, Université de Bretagne Occidentale, Institut Brestois en Santé Agro Matière (IBSAM), Faculté de médecine, 22, avenue Camille Desmoulins, 29200 Brest, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Flodrops
authors.affiliation: Inserm U1078-ECLA, Université de Bretagne Occidentale, Institut Brestois en Santé Agro Matière (IBSAM), Faculté de médecine, 22, avenue Camille Desmoulins, 29200 Brest, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Durand
authors.affiliation: Inserm U1078-ECLA, Université de Bretagne Occidentale, Institut Brestois en Santé Agro Matière (IBSAM), Faculté de médecine, 22, avenue Camille Desmoulins, 29200 Brest, France - Centre Hospitalier Universitaire de Brest, Boulevard Tanguy Prigent, 29200 Brest, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Chauveau
authors.affiliation: Inserm U1078-ECLA, Université de Bretagne Occidentale, Institut Brestois en Santé Agro Matière (IBSAM), Faculté de médecine, 22, avenue Camille Desmoulins, 29200 Brest, France.
authors.forename: Flaria
authors.initials: F
authors.lastname: El Khoury
authors.affiliation: Inserm U1078-ECLA, Université de Bretagne Occidentale, Institut Brestois en Santé Agro Matière (IBSAM), Faculté de médecine, 22, avenue Camille Desmoulins, 29200 Brest, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Le Jossic-Corcos
authors.affiliation: Inserm U1078-ECLA, Université de Bretagne Occidentale, Institut Brestois en Santé Agro Matière (IBSAM), Faculté de médecine, 22, avenue Camille Desmoulins, 29200 Brest, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Corcos
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D018450:Disease Progression; D006801:Humans; D009154:Mutation / Q000502:physiology; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D017381:Spliceosomes / Q000235:genetics / Q000502:physiology*
chemical_list: D012322:RNA Precursors; D012333:RNA, Messenger