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Conserved Regulation of Cardiac Calcium Uptake by Peptides Encoded in Small Open Reading Frames

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Science  06 Sep 2013:
Vol. 341, Issue 6150, pp. 1116-1120
DOI: 10.1126/science.1238802

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smORFing for Calcium

Genomes contain thousands of small open reading frames (smORFs), short DNA sequences coding for peptides of less than 100 amino acids. Magny et al. (p. 1116, published on 22 August) describe two smORF-encoded peptides of less than 30 amino acids regulating calcium transport and, hence, regular heart contraction, in the fruit fly Drosophila. These peptides seem to have been conserved for more than 550 million years in a range of species from flies to humans, where they have been implicated in severe heart diseases. Such conservation suggests that smORFs might be an ancient part of our functional genome.

Abstract

Small open reading frames (smORFs) are short DNA sequences that are able to encode small peptides of less than 100 amino acids. Study of these elements has been neglected despite thousands existing in our genomes. We and others previously showed that peptides as short as 11 amino acids are translated and provide essential functions during insect development. Here, we describe two peptides of less than 30 amino acids regulating calcium transport, and hence influencing regular muscle contraction, in the Drosophila heart. These peptides seem conserved for more than 550 million years in a range of species from flies to humans, in which they have been implicated in cardiac pathologies. Such conservation suggests that the mechanisms for heart regulation are ancient and that smORFs may be a fundamental genome component that should be studied systematically.

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