Title | Transcriptome-wide miR-155 binding map reveals widespread noncanonical microRNA targeting. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Loeb GB, Khan AA, Canner D, Hiatt JB, Shendure J, Darnell RB, Leslie CS, Rudensky AY |
Journal | Mol Cell |
Volume | 48 |
Issue | 5 |
Pagination | 760-70 |
Date Published | 2012 Dec 14 |
ISSN | 1097-4164 |
Keywords | 3' Untranslated Regions, Animals, Argonaute Proteins, Binding Sites, CD4-Positive T-Lymphocytes, Computational Biology, Down-Regulation, Gene Expression Profiling, Genes, Reporter, HEK293 Cells, Humans, Lymphocyte Activation, Mice, Mice, Knockout, MicroRNAs, Nucleotide Motifs, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, RNA, Messenger, Transcriptome, Transfection |
Abstract | MicroRNAs (miRNAs) are essential components of gene regulation, but identification of miRNA targets remains a major challenge. Most target prediction and discovery relies on perfect complementarity of the miRNA seed to the 3' untranslated region (UTR). However, it is unclear to what extent miRNAs target sites without seed matches. Here, we performed a transcriptome-wide identification of the endogenous targets of a single miRNA-miR-155-in a genetically controlled manner. We found that approximately 40% of miR-155-dependent Argonaute binding occurs at sites without perfect seed matches. The majority of these noncanonical sites feature extensive complementarity to the miRNA seed with one mismatch. These noncanonical sites confer regulation of gene expression, albeit less potently than canonical sites. Thus, noncanonical miRNA binding sites are widespread, often contain seed-like motifs, and can regulate gene expression, generating a continuum of targeting and regulation. |
DOI | 10.1016/j.molcel.2012.10.002 |
Alternate Journal | Mol. Cell |
PubMed ID | 23142080 |
PubMed Central ID | PMC3562697 |
Grant List | R01 NS081706 / NS / NINDS NIH HHS / United States GM07739 / GM / NIGMS NIH HHS / United States R37 AI034206 / AI / NIAID NIH HHS / United States / / Howard Hughes Medical Institute / United States T32 GM007739 / GM / NIGMS NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:11pm