Conserved microRNA targeting in Drosophila is as widespread in coding regions as in 3′UTRs

Michael Schnall-Levin, Yong Zhao, Norbert Perrimon, Bonnie Berger

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

Abstract

MicroRNAs (miRNAs) are a class of short noncoding RNAs that regulate protein-coding genes posttranscriptionally. In animals, most known miRNA targeting occurs within the 3′UTR of mRNAs, but the extent of biologically relevant targeting in the ORF or 5′ UTR of mRNAs remains unknown. Here, we develop an algorithm (MinoTar - miRNA ORF Targets) to identify conserved regulatory motifs within protein-coding regions and use it to estimate the number of preferentially conserved miRNA-target sites in ORFs. We show that, in Drosophila, preferentially conserved miRNA targeting in ORFs is as widespread as it is in 3′UTRs and that, while far less abundant, conserved targets in Drosophila 5′UTRs number in the hundreds. Using our algorithm, we predicted a set of high-confidence ORF targets and selected seven miRNA-target pairs from among these for experimental validation. We observed downregulation by the miRNA in five out of seven cases, indicating our approach can recover functional sites with high confidence. Additionally, we observed additive targeting by multiple sites within a single ORF. Altogether, our results demonstrate that the scale of biologically important miRNA targeting in ORFs is extensive and that computational tools such as ours can aid in the identification of such targets. Further evidence suggests that our results extend to mammals, but that the extent of ORF and 5′UTR targeting relative to 3′UTR targeting may be greater in Drosophila.

Original languageEnglish
Pages (from-to)15751-15756
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number36
DOIs
StatePublished - 7 Sep 2010
Externally publishedYes

Keywords

  • Comparative genomics
  • Target prediction

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