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Genes Cells. 2002 Feb;7(2):133-41.

Regulation of alternative splicing of alpha-actinin transcript by Bruno-like proteins.

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1
Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma 630-0101, Japan.

Abstract

BACKGROUND:

The Bruno-like or CELF proteins, such as mammalian CUGBP1 and Etr-3, Xenopus EDEN-BP, and Drosophila Bruno (Bru), are regulators of gene expression at the post-transcriptional level, and contain three RNA-recognition motifs (RRMs). It has been shown that mammalian CUGBP1 and Etr-3 regulate alternative splicing of cardiac troponin T pre-mRNA via binding to CUG-triplet repeats.

RESULTS:

Using in vitro selection and UV-crosslinking experiments, we found that zebrafish Bruno-like proteins bound to repeat elements of uridine and purine (termed UREs). It is known that non-muscle (NM) and smooth muscle (SM) exons of the rat alpha-actinin gene are used in a mutually exclusive manner. Transfection experiments in mammalian cells showed that zebrafish Brul and Etr-3 induced the muscle-specific splicing of rat alpha-actinin pre-mRNA via binding to the URE at the branch point upstream of the NM exon. In contrast, zebrafish Etr-1 promoted skipping of both the NM and SM exons in a manner which was not dependent on URE-binding.

CONCLUSIONS:

Our results showed that Bruno-like proteins bind to UREs and regulate the alternative splicing of alpha-actinin pre-mRNA. Members of the Bruno family play multiple roles in splicing regulation.

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