Hong, X., Hammell, M., Ambros, V., Cohen, S. M. (September 2009) Immunopurification of Ago1 miRNPs selects for a distinct class of microRNA targets. Proceedings of the National Academy of Sciences of the United States of America, 106 (35). pp. 15085-90. ISSN 0027-8424
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Abstract
microRNAs comprise a few percent of animal genes and have been recognized as important regulators of a diverse range of biological processes. Understanding the biological functions of miRNAs requires effective means to identify their targets. Combined efforts from computational prediction, miRNA over-expression or depletion, and biochemical purification have identified thousands of potential miRNA-target pairs in cells and organisms. Complementarity to the miRNA seed sequence appears to be a common principle in target recognition. Other features, including miRNA-target duplex stability, binding site accessibility, and local UTR structure might affect target recognition. Yet computational approaches using such contextual features have yielded largely nonoverlapping results and experimental assessment of their impact has been limited. Here, we compare two large sets of miRNA targets: targets identified using an improved Ago1 immunopurification method and targets identified among transcripts up-regulated after Ago1 depletion. We found surprisingly limited overlap between these sets. The two sets showed enrichment for target sites with different molecular, structural and functional properties. Intriguingly, we found a strong correlation between UTR length and other contextual features that distinguish the two groups. This finding was extended to all predicted microRNA targets. Distinct repression mechanisms could have evolved to regulate targets with different contextual features. This study reveals a complex relationship among different features in miRNA-target recognition and poses a new challenge for computational prediction.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Animals Argonaute Proteins Drosophila Proteins/*genetics Drosophila melanogaster/*genetics Eukaryotic Initiation Factors/*genetics Genome-Wide Association Study MicroRNAs/chemistry/genetics/immunology/*isolation & purification Nucleic Acid Conformation RNA, Messenger/genetics Systems Biology/methods Transcription, Genetic Up-Regulation |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > argonaute proteins bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA |
| CSHL Authors: | |
| Communities: | CSHL labs > Hammell M. lab |
| Depositing User: | Matt Covey |
| Date: | 1 September 2009 |
| Date Deposited: | 06 Nov 2014 17:48 |
| Last Modified: | 05 Jan 2018 20:04 |
| PMCID: | PMC2728611 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/30882 |
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