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MBE Advance Access published online on September 21, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm195
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© The Author 2007. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Article

Human TRIM71 and Its Nematode Homologue are Targets of let-7 MicroRNA and Its Zebrafish Orthologue is Essential for Development

You-Chin Lin1,6, Li-Ching Hsieh1,2,6, Ming-Wei Kuo3, John Yu1,3, Huan-Hsien Kuo1, Wan-Lin Lo1, Ruey-Jen Lin1, Alice L. Yu1,4,7,9 and Wen-Hsiung Li1,5,7,8

1 Genomics Research Center, Academia Sinica, Taipei 115, Taiwan
2 Institute of Information Science, Academia Sinica, Taipei 115, Taiwan
3 Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan
4 Department of Pediatrics Hematology-Oncology, University of California in San Diego, San Diego, CA 92103-8447, USA
5 Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637, USA
6 These authors contributed equally to this work
7 These authors contributed equally to this work

8 Dr W-H Li: whli{at}uchicago.edu

9 Dr AL Yu: aliceyu{at}ucsd.edu

Received for publication June 15, 2007. Revision received August 30, 2007. Accepted for publication September 3, 2007.

Animal microRNAs (miRNAs) are short RNAs that function as posttranscriptional regulators of gene expression by binding to the target mRNAs. Noting that some miRNAs are highly conserved in evolution, we explored the possibility of evolutionary conservation of their targets. We identified human orthologues of experimentally verified let-7 miRNA target genes in C. elegans and used the luciferase reporter system to examine whether these human genes are still the targets of let-7 miRNA. We found that in some cases the miRNA-target relationship has indeed been conserved in human. Interestingly, human TRIM71, an orthologue of C. elegans let-7-target lin-41 gene, can be repressed by hsa-let-7a and by hsa-let-7c. This repression was abolished when both predicted let-7 target sites of TRIM71 were mutated. Moreover, the zebrafish lin-41 orthologue was also repressed by let-7 to a similar degree as was TRIM71. When the expression of zebrafish lin-41 orthologue was silenced by microinjection of RNAi or morpholino into zebrafish zygotes, retarded embryonic development was observed, providing direct evidence for an essential role of lin-41 in zebrafish development. Taken together, our results suggest that the regulation of TRIM71 expression by let-7 has been evolutionarily conserved and that TRIM71 likely plays an important role in development.

Key Words: TRIM71 • lin-41 • let-7 • microRNA target


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Y.-C. Lin, M.-W. Kuo, J. Yu, H.-H. Kuo, R.-J. Lin, W.-L. Lo, and A. L. Yu
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[Abstract] [Full Text] [PDF]


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