Tissue-specific RNA splicing generates an ankyrin-like domain that affects the dimerization and DNA-binding properties of a bHLH protein.
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.
Klein
E S
ES
Eukaryotic Regulatory Biology Program, Department and School of Medicine, La Jolla, California 92093-0648.
Simmons
D M
DM
Swanson
L W
LW
Rosenfeld
M G
MG
D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D011247:Pregnancy; D012326:RNA Splicing; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D015533:Transcriptional Activation
D017487:Ankyrins; D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D004268:DNA-Binding Proteins; C079409:REB beta protein, rat