A Family of Human RNA-binding Proteins Related to theDrosophila Bruno Translational Regulator

Peter J Good,Qingdan Chen,Stephen J Warner,Dina C Herring

doi:10.1074/jbc.m003083200

Abstract

The post-transcriptional regulation of gene expression by RNA-binding proteins is an important element in controlling both normal cell functions and animal development. The diverse roles are demonstrated by the Elav family of RNA-binding proteins, where various members have been shown to regulate several processes involving mRNA. We have identified another family of RNA-binding proteins distantly related to the Elav family but closely related to Bruno, a translational regulator in Drosophila melanogaster. In humans, six Bruno-like genes have been identified, whereas other species such as Drosophila, Xenopus laevis, and Caenorhabditis elegans have at least two members of this family, and related genes have also been detected in plants and ascidians. The human BRUNOL2 and BRUNOL3 are 92% identical in the RNA-binding domains, although the BRUNOL2 gene is expressed ubiquitously whereas BRUNOL3 is expressed predominantly in the heart, muscle, and nervous system. Both of these proteins bind the same target RNA, the Bruno response element. The RNA-binding domain that recognizes the Bruno response element is composed of two consecutive RNA recognition motifs at the amino terminus of vertebrate Bruno protein. The possible involvement of the Bruno family of proteins in the CUG repeat expansion disease myotonic dystrophy is discussed.

Highlights

Proteins that bind RNA have many functions in the posttranscriptional regulation of gene expression
The BRUNOL2 protein is identical to the CUG-binding protein 1 (CUGBP1), an RNAbinding proteins (RBPs) that binds to CUG repeats and is implicated in the etiology of the triplet repeat expansion disease myotonic dystrophy [42]
Bruno-like Genes—The Xenopus brunol-1 gene was described as a marker of the embryonic nervous system and encodes a putative RNA-binding protein [40, 58]. This cDNA was most similar to the Elav family of RBPs, this similarity was primarily because of highly conserved residues in the RNA recognition motif (RRM)

Summary

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The BRUNOL2 and BRUNOL3 proteins bind to the same RNA sequence as the Drosophila Bruno protein, demonstrating a conservation of both protein sequence and RNA binding specificity This binding occurs through the first two consecutive RRMs. The BRUNOL2 protein is identical to the CUGBP1, an RBP that binds to CUG repeats and is implicated in the etiology of the triplet repeat expansion disease myotonic dystrophy [42]. The BRUNOL2 protein is identical to the CUGBP1, an RBP that binds to CUG repeats and is implicated in the etiology of the triplet repeat expansion disease myotonic dystrophy [42] Members of this gene family may be involved in human disease as well as differentiation of specific cell types

EXPERIMENTAL PROCEDURES

TABLE II Oligonucleotide sequences

RESULTS

Unigene contiga

DISCUSSION