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Updated: May 21, 2026

A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells
Published on: June 16, 2022
Functional interplay between RNA-binding protein HuR and microRNAs
Subramanya Srikantan1, Kumiko Tominaga, Myriam Gorospe
1Laboratory of Molecular Biology and Immunology, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA.
Abstract:
The mammalian RNA-binding protein (RBP) HuR associates with numerous mRNAs encoding proteins with roles in cell division, cell survival, immune response, and differentiation. HuR was known to stabilize many of these mRNAs and/or modulated their translation, but the molecular processes by which HuR affected the fate of target mRNAs was largely unknown. Evidence accumulated over the past five years has revealed that the influence of HuR on many bound transcripts depends on HuR's interplay with microRNAs which associate with the same mRNAs. Here, we review the interactions of HuR and microRNAs - both competitive and cooperative - that govern expression of shared target mRNAs. Competition between HuR and microRNAs typically results in enhanced gene expression if the HuR-mRNA interaction prevails, and in repression if the microRNA remains associated. Cooperation between HuR and microRNAs leads to lower expression of the shared mRNA. We also describe the regulation of HuR levels by microRNAs as well as the regulation of microRNA levels by HuR. Finally, we discuss transcriptome-wide analyses of HuR-bound mRNAs with neighboring microRNA sites, and review the emerging mechanisms whereby microRNAs confer versatility and robustness to the post-transcriptional outcomes of HuR targets.
Insights
The RNA-binding protein HuR interacts with microRNAs to control gene expression. These interactions can either enhance or repress the expression of target messenger RNAs (mRNAs), influencing cellular processes.
Area of Science:
- Molecular Biology
- Post-transcriptional Regulation
- Gene Expression Control
Background:
- The RNA-binding protein HuR (Human antigen R) binds to numerous messenger RNAs (mRNAs) involved in critical cellular functions.
- HuR's known roles include stabilizing mRNAs and modulating translation, but the precise mechanisms were unclear.
- Recent findings highlight the crucial interplay between HuR and microRNAs in determining mRNA fate.
Purpose of the Study:
- To review the complex interactions between HuR and microRNAs.
- To elucidate how these interactions govern the expression of shared target mRNAs.
- To discuss the reciprocal regulation between HuR and microRNAs.
Main Methods:
- Literature review of recent evidence on HuR-microRNA interactions.
- Analysis of competitive and cooperative binding mechanisms.
- Discussion of transcriptome-wide data and emerging regulatory pathways.
Main Results:
- HuR and microRNA interactions can be competitive or cooperative, leading to differential gene expression outcomes.
- Competition typically enhances gene expression if HuR binding dominates, or represses it if microRNA binding prevails.
- Cooperation between HuR and microRNAs generally results in decreased expression of shared target mRNAs.
Conclusions:
- MicroRNAs significantly influence HuR's post-transcriptional regulation of target mRNAs.
- The interplay between HuR and microRNAs provides versatility and robustness to gene expression.
- Understanding these interactions is key to comprehending cellular regulation and disease processes.
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