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Intracellular and extracellular microRNA: An update on localization and biological role
Julia A Makarova1, Maxim U Shkurnikov2, Daniel Wicklein3
1Hertsen Moscow Oncology Research Institute, Branch of the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, 125284, Moscow, Russian Federation; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russian Federation.
MicroRNAs (miRNAs) are small RNAs that regulate gene expression. This review explores their surprising locations within cells and their roles as signaling molecules outside the cell, potentially serving as disease biomarkers.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression, mediating post-transcriptional gene silencing (PTGS).
- miRNAs, along with Argonaute (AGO) proteins, form RNA-induced silencing complexes (RISC), crucial for gene regulation.
- The intracellular localization and diverse functions of miRNAs and RISC were not fully understood until recently.
Purpose of the Study:
- To review the emerging understanding of miRNA and RISC localization and function within cells.
- To explore the extracytoplasmic roles of miRNAs, including their potential as signaling molecules.
- To discuss miRNA secretion mechanisms and their role in intercellular communication.
Main Methods:
- Literature review of studies investigating miRNA and RISC localization.
- Analysis of research on miRNA functions in various cellular compartments.
- Examination of findings related to cell-free miRNAs and their implications.
Main Results:
- PTGS primarily occurs on endoplasmic reticulum (ER) membranes, challenging the traditional cytoplasmic model.
- miRNAs are found in diverse cellular compartments, including the nucleus, nucleolus, and mitochondria, regulating key processes.
- Cell-free miRNAs in biological fluids suggest roles in cell signaling and potential as disease biomarkers.
Conclusions:
- miRNA and RISC localization is more complex and widespread than previously assumed.
- Extracellular miRNAs represent a novel mechanism for intercellular communication and disease diagnostics.
- Further research into miRNA secretion and function is warranted.
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