title: Multiple novel transcription initiation sites for NRG1.
abstract: The large neuregulin 1 gene (NRG1) has been mapped to a 1.125 Mb region on chromosome 8p11-21. Three major forms of NRG1 (types I-III), all with distinct amino-termini encoded by unique 5'-exons, have been described. We report here the discovery of nine novel NRG1 exons, including six alternative 5'-exons, increasing the number of potential promoters in NRG1 from three to nine. The novel transcripts of NRG1 described here use the novel 5'-exons which are either coding or non-coding. The functional relevance of the predicted proteins they encode has not been evaluated. Three of the novel 5'-exons are well conserved in syntenic rat and mouse sequences; they encode proteins with novel amino-termini, here termed types IV-VI. NRG1 plays a central role in neural development and is most likely involved in regulation of synaptic plasticity, or how the brain responds or adapts to the environment. The unusually complex gene structure may facilitate spatial and temporal regulation of NRG1 expression, fine-tune NRG1 protein function at different stages during development of the nervous system, and adapt responses to the environment in the adult brain.
authors.affiliation: deCODE Genetics, Sturlugata 8, IS-101 Reykjavik, Iceland. vstein@decode.is
authors.forename: Valgerdur
authors.initials: V
authors.lastname: Steinthorsdottir
authors.forename: Hreinn
authors.initials: H
authors.lastname: Stefansson
authors.forename: Shyamali
authors.initials: S
authors.lastname: Ghosh
authors.forename: Birgitta
authors.initials: B
authors.lastname: Birgisdottir
authors.forename: Soley
authors.initials: S
authors.lastname: Bjornsdottir
authors.forename: Anne Charlotte
authors.initials: AC
authors.lastname: Fasquel
authors.forename: Olafur
authors.initials: O
authors.lastname: Olafsson
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gulcher
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D030561:Databases, Nucleic Acid; D005091:Exons / Q000235:genetics; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020890:Neuregulin-1; D051381:Rats; D017422:Sequence Analysis, DNA; D024363:Transcription Initiation Site
chemical_list: D018076:DNA, Complementary; C094131:NRG1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1