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Regulation of alternative splicing of α‐actinin transcript by Bruno‐like proteins
Author(s) -
Suzuki Hitoshi,
Jin Yui,
Otani Hifumi,
Yasuda Kunio,
Inoue Kunio
Publication year - 2002
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1356-9597.2001.00506.x
Subject(s) - biology , rna splicing , exon , alternative splicing , zebrafish , rna binding protein , sr protein , intron , gene , microbiology and biotechnology , messenger rna , gene expression , rna , genetics
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 α‐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 α‐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 α‐actinin pre‐mRNA. Members of the Bruno family play multiple roles in splicing regulation.