PUBLICATION
Dispatched Homolog 2 is targeted by miR-214 through a combination of three weak microRNA recognition sites
- Authors
- Li, N., Flynt, A.S., Kim, H.R., Solnica-Krezel, L., and Patton, J.G.
- ID
- ZDB-PUB-080630-19
- Date
- 2008
- Source
- Nucleic acids research 36(13): 4277-4285 (Journal)
- Registered Authors
- Flynt, Alex, Kim, Rosemary, Li, Nan, Patton, James G., Solnica-Krezel, Lilianna
- Keywords
- none
- MeSH Terms
-
- Animals
- Membrane Proteins/genetics*
- Base Pairing
- MicroRNAs/chemistry
- MicroRNAs/metabolism*
- Zebrafish/anatomy & histology
- Zebrafish/embryology
- Zebrafish/genetics*
- Embryo, Nonmammalian/anatomy & histology
- RNA Interference*
- Zebrafish Proteins/genetics*
- 3' Untranslated Regions/chemistry
- PubMed
- 18583362 Full text @ Nucleic Acids Res.
Citation
Li, N., Flynt, A.S., Kim, H.R., Solnica-Krezel, L., and Patton, J.G. (2008) Dispatched Homolog 2 is targeted by miR-214 through a combination of three weak microRNA recognition sites. Nucleic acids research. 36(13):4277-4285.
Abstract
MicroRNAs (miRNAs) regulate gene expression by inhibiting translation of target mRNAs through pairing with miRNA recognition elements (MREs), usually in 3' UTRs. Because pairing is imperfect, identification of bona fide mRNA targets presents a challenge. Most target recognition algorithms strongly emphasize pairing between nucleotides 2-8 of the miRNA (the 'seed' sequence) and the mRNA but adjacent sequences and the local context of the 3' UTR also affect targeting. Here, we show that dispatched 2 is a target of miR-214. In zebrafish, dispatched 2 is expressed in the telencephalon and ventral hindbrain and is essential for normal zebrafish development. Regulation of dispatched 2 by miR-214 is via pairing with three, noncanonical, weak MREs. By comparing the repression capacity of GFP reporters containing different dispatched 2 sequences, we found that a combination of weak sites, which lack canonical seed pairing, can effectively target an mRNA for silencing. This finding underscores the challenge that prediction algorithms face and emphasizes the need to experimentally validate predicted MREs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping