In silico analysis of neuregulin 1 evolution in vertebrates

Abstract

NRG1 (neuregulin 1) belongs to the NRG family of EGF (epidermal growth factor)-like signalling molecules involved in cell-cell communication during development and disease. It plays important roles in the developing tissues of the nerves, heart and mammary glands. Particularly in neurobiology, NRG1 signalling is associated with synaptic transmission, myelination of Schwann cells and the human disease of schizophrenia. Many different isoforms of NRG1 make the molecule highly sophisticated in biological activities and a great diversity of in vivo functions. The nervous system is a common trait in all bilateria (higher animals), but based on the BLAST information from the currently available databases it appears that NRG1 orthologues can only be identified in vertebrates. The gene was analysed in silico for type I-IV CDSs (coding sequences) from ten vertebrate genomes. The gene loci, structures of coding-intronic sequences, ClustalW program analyses, phylogenetic trees and conserved motifs in ecto- and cyto-plasmic domains were analysed and compared. Here, we conclude that non-mammalian vertebrates mainly carry type I (may have evolved a spacer different from mammalian isoforms), II and III NRG1s. The type IV NRG1 N-terminal CDSs can be identified from most of the mammalian genomes studied; however, the corresponding rodent sequences lack the start codon. The evolutionary conservation of a CDS59-CDS24-CDS103 domain, intracellular phosphorylation sites and bipartite nuclear localization signals is of physiological significance.

Neuregulin-1, a potential therapeutic target for cardiac repair

“…NRG1 is the most characteristic member of the neuregulin family ( Huang et al, 2015a ). The NRG1 gene is found on chromosome 8 in humans and mice and on chromosome 16 in rats ( Falls, 2003 ; Chou and Ozaki, 2010 ). NRG-1 encodes 21 exons ( Peles et al, 1992 ; Steinthorsdottir et al, 2004 ) and generates 31 potential protein isoforms ( Mei and Xiong, 2008 ).…”

Partial loss‐of‐function variant in neuregulin 1 identified in family with heritable peripheral neuropathy

“…Through different promoters and alternative messenger RNA (mRNA) splicing, the Nrg1 gene encodes more than 30 different isoforms, which are further modified by posttranslational processing (Falls, 2003; Hu et al, 2006; La Marca et al, 2011; Willem et al, 2006). In humans, the NRG1 gene has distinct promoters that generate six main classes of isoforms (types I, II, III, IV, V, and VI) that have different N‐terminal regions but share a common EGF‐related domain that activates ErbB receptors (Chou & Ozaki, 2010). While types IV–VI are not present in all vertebrates, the types I, II, and III isoforms are widely conserved among vertebrates, and mutational studies in mouse and zebrafish have identified Nrg1 type III signals as essential regulators of Schwann cell development and myelination (Perlin et al, 2011; Wolpowitz et al, 2000).…”

Neuregulin‑1, a microvascular endothelial‑derived protein, protects against myocardial ischemia‑reperfusion injury (Review)

“…Structure and isoforms of NRG-1. As a member of the Neuregulin family of growth factors, NRG-1, encoded by a gene spanning 2.4 million base pairs in mice and 2.6 million base pairs in humans and rats, is located on chromosome 8 in humans and mice, and on chromosome 16 in rats (9,10). The 6 known types of NRG-1 proteins (types I-VI) are classified by 6 different transcriptional initiation sites, and alternative splicing of the NRG-1 gene produces 33 different isoforms in humans (11,12).…”