October 17, 2024
What is MicroRNAs (miRNAs)?
MicroRNAs (miRNAs) are small, non-coding RNA molecules, typically about 20–25 nucleotides in length, that play a crucial role in regulating gene expression in plants, animals, and some viruses. They function primarily by binding to messenger RNA (mRNA) and either degrading the mRNA or inhibiting its translation into proteins.
Key Characteristics of microRNAs:
- Size and Structure:
- miRNAs are small, single-stranded RNA molecules, usually around 20–25 nucleotides long.
- They are derived from longer precursor molecules (pri-miRNA) that fold into a hairpin loop structure, which is processed into mature miRNA.
- Function:
- Gene Regulation: miRNAs regulate gene expression by binding to complementary sequences in the 3′ untranslated region (3′ UTR) of target mRNA molecules. This either leads to the degradation of the mRNA or inhibits its translation, thereby reducing the production of proteins.
- Post-transcriptional Regulation: miRNAs act after the transcription process (where DNA is converted into RNA), controlling the stability and translation of mRNA.
- Biogenesis:
- Primary miRNA (pri-miRNA) is transcribed from DNA, often by RNA polymerase II.
- The pri-miRNA is processed in the nucleus by a protein complex called Drosha into a precursor miRNA (pre-miRNA), which forms a hairpin structure.
- The pre-miRNA is then exported to the cytoplasm, where it is further cleaved by the Dicer enzyme into a mature miRNA.
- The mature miRNA is incorporated into the RNA-induced silencing complex (RISC), which directs it to its target mRNA.
- Mechanism of Action:
- miRNAs guide the RISC to complementary sequences on target mRNAs.
- If the match between miRNA and mRNA is perfect, the mRNA is cleaved and degraded.
- If the match is imperfect, the translation of the mRNA is repressed, reducing protein production.
- Biological Roles:
- Development: miRNAs are involved in regulating various aspects of development, such as cell differentiation, proliferation, and apoptosis (programmed cell death).
- Cancer: Dysregulation of miRNAs has been linked to the development of various cancers. Some miRNAs function as tumor suppressors, while others act as oncogenes.
- Immune Function: miRNAs help regulate immune responses by controlling the expression of genes involved in immune cell development and activation.
- Neurological Function: miRNAs play roles in the development and function of the nervous system, and dysregulation has been implicated in neurodegenerative diseases.
- Clinical Applications:
- Biomarkers: miRNAs are being studied as potential biomarkers for diseases, especially cancers, due to their stability in blood and other body fluids.
- Therapeutics: Targeting miRNAs for therapy is a promising area of research. miRNA-based therapies aim to inhibit or replace specific miRNAs that are dysregulated in diseases like cancer, cardiovascular diseases, and viral infections.
Examples of microRNAs:
- miR-21: Often upregulated in many cancers, contributing to tumor growth and progression.
- Let-7: Functions as a tumor suppressor, and its downregulation is associated with various cancers.