Evidence that microRNAs are associated with translating messenger RNAs in human cells
Patricia A Maroney1, Yang Yu, Jesse Fisher
1Center for RNA Molecular Biology and Department of Biochemistry, Case Western Reserve University School of Medicine, W127 10900 Euclid Avenue, Cleveland, Ohio 44106-4973, USA.
Nature Structural & Molecular Biology
|November 28, 2006
Abstract:
MicroRNAs (miRNAs) regulate gene expression post-transcriptionally by binding the 3' untranslated regions of target mRNAs. We examined the subcellular distribution of three miRNAs in exponentially growing HeLa cells and found that the vast majority are associated with mRNAs in polysomes. Several lines of evidence indicate that most of these mRNAs, including a known miRNA-regulated target (KRAS mRNA), are actively being translated.
Insights
MicroRNAs (miRNAs) associate with actively translated messenger RNAs (mRNAs) in cell polysomes. This finding suggests miRNAs play a direct role in regulating gene expression during active protein synthesis.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression.
- miRNAs function by binding to the 3' untranslated regions of target messenger RNAs (mRNAs).
- Understanding miRNA localization provides insights into their regulatory mechanisms.
Purpose of the Study:
- To investigate the subcellular distribution of specific microRNAs in HeLa cells.
- To determine the association of microRNAs with actively translated mRNAs.
- To explore the functional relevance of miRNA localization within polysomes.
Main Methods:
- Subcellular fractionation of exponentially growing HeLa cells.
- Isolation and analysis of polysomal fractions.
- Detection and quantification of specific microRNAs within cellular compartments.
Main Results:
- The majority of three specific microRNAs were found associated with polysomes.
- Polysomal association indicates co-localization with actively translating mRNAs.
- Evidence confirmed that these associated mRNAs, including KRAS mRNA, are undergoing translation.
Conclusions:
- MicroRNAs are predominantly localized to polysomes in actively growing cells.
- This localization suggests a direct role for miRNAs in regulating gene expression during active translation.
- The findings support a model where miRNAs interact with mRNAs undergoing protein synthesis.
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