title: An 8-bp deletion in mNOTCH4 intron 10 leads to its retention in mRNA and to synthesis of a truncated protein.
abstract: Notch signaling participates in the development of multicellular organisms by maintaining self-renewal potential or inducing differentiation of numerous tissues. In this study, we characterized Notch4, the evolutionary most distant and least studied Notch family member. We identified a Notch4 inter-strain polymorphism with a previously undescribed mRNA variant. This longer Notch4 mRNA, which represented up to one-third of total Notch4 mRNA, resulted from intron 10 retention. Analysis of Notch4 intron 10 revealed that an 8-bp deletion, reducing its length from 68 to 60 bp, strictly correlated with its retention. Further experiments demonstrated that intron length was the only cause of the mis-splicing. Moreover, this mRNA variant resulted in a truncated protein containing half the extracellular domain of Notch4, including the ligand-binding domain.
authors.affiliation: INSERM U561, Hôpital St. Vincent de Paul, 82 Avenue Denfert Rochereau, Paris 75014, France. auffray@necker.fr
authors.forename: Cédric
authors.initials: C
authors.lastname: Auffray
authors.forename: Régis
authors.initials: R
authors.lastname: Gayon
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Benraiss
authors.forename: Nicolas
authors.initials: N
authors.lastname: Martin
authors.forename: Ingrid
authors.initials: I
authors.lastname: Laurendeau
authors.forename: Julie
authors.initials: J
authors.lastname: Garaud
authors.forename: Bruno
authors.initials: B
authors.lastname: Lucas
authors.forename: Christian
authors.initials: C
authors.lastname: Boitard
authors.forename: Patricia
authors.initials: P
authors.lastname: Krief
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D007438:Introns / Q000235:genetics*; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000096:biosynthesis / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000074562:Receptor, Notch4; D051880:Receptors, Notch; C073572:Notch4 protein, mouse