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Challenging Cellular Homeostasis: Spatial and Temporal Regulation of miRNAs
Naomi van Wijk1, Keren Zohar1, Michal Linial1
1Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, Faculty of Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Abstract:
Mature microRNAs (miRNAs) are single-stranded non-coding RNA (ncRNA) molecules that act in post-transcriptional regulation in animals and plants. A mature miRNA is the end product of consecutive, highly regulated processing steps of the primary miRNA transcript. Following base-paring of the mature miRNA with its mRNA target, translation is inhibited, and the targeted mRNA is degraded. There are hundreds of miRNAs in each cell that work together to regulate cellular key processes, including development, differentiation, cell cycle, apoptosis, inflammation, viral infection, and more. In this review, we present an overlooked layer of cellular regulation that addresses cell dynamics affecting miRNA accessibility. We discuss the regulation of miRNA local storage and translocation among cell compartments. The local amounts of the miRNAs and their targets dictate their actual availability, which determines the ability to fine-tune cell responses to abrupt or chronic changes. We emphasize that changes in miRNA storage and compactization occur under induced stress and changing conditions. Furthermore, we demonstrate shared principles on cell physiology, governed by miRNA under oxidative stress, tumorigenesis, viral infection, or synaptic plasticity. The evidence presented in this review article highlights the importance of spatial and temporal miRNA regulation for cell physiology. We argue that limiting the research to mature miRNAs within the cytosol undermines our understanding of the efficacy of miRNAs to regulate cell fate under stress conditions.
Insights
Cellular regulation involves microRNAs (miRNAs), which control gene expression. This review highlights how miRNA storage and movement impact cell dynamics and stress responses, revealing a crucial layer of biological control.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Mature microRNAs (miRNAs) are key regulators of gene expression at the post-transcriptional level.
- Hundreds of miRNAs orchestrate vital cellular processes like development, apoptosis, and inflammation.
- Current research often overlooks the spatial dynamics and accessibility of miRNAs within cells.
Purpose of the Study:
- To explore the underappreciated role of miRNA localization and translocation in cellular regulation.
- To discuss how miRNA storage and accessibility influence cellular responses to stress.
- To emphasize the significance of spatial and temporal miRNA regulation in cell fate determination.
Main Methods:
- This review synthesizes existing literature on miRNA processing, function, and cellular localization.
- It analyzes studies investigating miRNA dynamics under various cellular conditions, including stress.
- The review integrates findings on miRNA involvement in oxidative stress, tumorigenesis, viral infection, and synaptic plasticity.
Main Results:
- Cellular regulation is influenced by the local storage and translocation of miRNAs between cellular compartments.
- Changes in miRNA compactization and localization are observed under induced stress.
- Shared physiological principles governed by miRNAs are evident across diverse conditions like oxidative stress and viral infections.
Conclusions:
- Spatial and temporal regulation of miRNAs is critical for overall cell physiology.
- Understanding miRNA dynamics beyond the cytosol is essential for comprehending their role in cell fate.
- Considering miRNA accessibility and localization provides a more complete picture of their regulatory efficacy, especially under stress.
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