title: 3'-UTR-dependent regulation of mRNA turnover is critical for differential distribution patterns of cyclic gene mRNAs.
abstract: Somite segmentation, a prominent periodic event in the development of vertebrates, is instructed by cyclic expression of several genes, including Hes7 and Lunatic fringe (Lfng). Transcriptional regulation accounts for the cyclic expression. In addition, because the expression patterns vary in a cycle, rapid turnover of mRNAs should be involved in the cyclic expression, although its contribution remains unclear. Here, we demonstrate that 3'-UTR-dependent rapid turnover of Lfng and Hes7 plays a critical role in their dynamic expression patterns. The regions active in the transcription of Lfng and Hes7 are wholly overlapped in the posterior presomitic mesoderm (PSM) of the mouse embryo. However, their distribution patterns are slightly different; Hes7 mRNA shows a broader distribution pattern than Lfng mRNA in the posterior PSM. Lfng mRNA is less stable than Hes7 mRNA, where their 3'-UTRs are responsible for the different stability. Using transgenic mice expressing Venus under the control of the Hes7 promoter, which leads to cyclic transcription in the PSM, we reveal that the Lfng 3'-UTR provides the narrow distribution pattern of Lfng mRNA, whereas the Hes7 3'-UTR contributes the relatively broad distribution pattern of Hes7 mRNA. Thus, we conclude that 3'-UTR-dependent mRNA stability accounts for the differential distribution patterns of Lfng and Hes7 mRNA. Our findings suggest that 3'-UTR-dependent regulation of mRNA turnover plays a crucial role in the diverse patterns of mRNA distribution during development.
authors.affiliation: Laboratory of Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Nitanda
authors.forename: Takaaki
authors.initials: T
authors.lastname: Matsui
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Matta
authors.forename: Aya
authors.initials: A
authors.lastname: Higami
authors.forename: Kenji
authors.initials: K
authors.lastname: Kohno
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Nakahata
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Bessho
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D015153:Blotting, Western; D019521:Body Patterning; D005260:Female; D018507:Gene Expression Regulation, Developmental; D016695:Glycosyltransferases / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D019170:Somites / Q000166:cytology / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D051792:Basic Helix-Loop-Helix Proteins; D016695:Glycosyltransferases; D012333:RNA, Messenger; C430525:Hes7 protein, mouse; C498392:Lfng protein, mouse
keywords: 3′-UTR; Hes7; Lfng; mRNA distribution; segmentation clock