Tissue-specific RNA splicing generates an ankyrin-like domain that affects the dimerization and DNA-binding properties of a bHLH protein

• Published in: Genes & development Vol. 7; no. 1; pp. 55 - 71
• Main Authors: KLEIN, E. S, SIMMONS, D. M, SWANSON, L. W, ROSENFELD, M. G
• Format: Journal Article
• Language: English
• Published: Cold Spring Harbor, NY Cold Spring Harbor Laboratory 1993
• Subjects: Amino Acid Sequence; Animals; Ankyrins - genetics; Ankyrins - metabolism; Base Sequence; Basic Helix-Loop-Helix Transcription Factors; Biological and medical sciences; Cell Line; Cercopithecus aethiops; Cloning, Molecular; DNA; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Mice; Mice, Inbred C3H; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Organ Specificity - genetics; Pregnancy; Rats; Rats, Sprague-Dawley; RNA Splicing; Sequence Homology, Amino Acid; Transcription. Transcription factor. Splicing. Rna processing; Transcriptional Activation; Alternative splicing; Rat; Nucleotide sequence; Rodentia; DNA binding protein; Tissue specificity; Homology; Molecular interaction; Gene expression; Vertebrata; Regulation(control); Mammalia; Development; Chromosome DNA; Transcription factor
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.7.1.55

mRNAs encoding two rat bHLH proteins, referred to as REB alpha and REB beta, have been identified as alternatively spliced transcripts derived from a single genomic locus. Alternative RNA processing events results in tissue-specific differences in the ratios of these two mRNAs. Although it exhibits a highly enriched level of expression in the developing neural tube, the REB gene is expressed at variable levels in many organs of the mature animal. The REB alpha sequence contains a region characterized by a leucine heptad repeat that is situated amino-terminal of the carboxy-terminally located bHLH domain. REB beta is identical to REB alpha except for a 24-amino-acid insertion in the leucine heptad repeat that results from the inclusion of an additional 72-bp exon in the REB beta transcript. As a consequence of this insertion, REB beta exhibits a markedly diminished capacity to bind to cognate E-box-binding sites and to form homodimers and heterodimers with other members of the bHLH gene family. Analysis of the 24-amino-acid REB beta-specific insert revealed that it mediates an inhibitory function and exhibits a significant degree of sequence similarity to ankyrin-like repeats. It is proposed that this tissue-specific pattern of REB RNA splicing is involved in the determination of corresponding tissue-specific combinations of heterodimeric complexes of ubiquitous and tissue-restricted bHLH proteins. Thus, REB alpha and REB beta represent a novel example of a regulated formation of an ankyrin-like domain within a bHLH protein, thereby mediating control of protein-protein interactions.