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MicroRNA

life science Maturity 9-11 Next article →

MicroRNAs, often called miRNAs, are tiny, single-stranded molecules that act as regulators within cells. They are non-coding RNA molecules, meaning they do not provide instructions to build proteins themselves. Instead, they control how other genes are expressed through a process called RNA silencing. Each miRNA is very small, typically containing only 21 to 23 nucleotides.

MiRNA
MiRNA

These molecules are found in plants, animals, and even some viruses. They are essential for managing the complex biological processes that keep organisms functioning correctly.

The mechanism of miRNA action begins when a miRNA finds a target messenger RNA, or mRNA. The mRNA is the molecule that carries instructions from DNA to build proteins. A miRNA identifies its target by base-pairing with a complementary sequence on the mRNA. In animals, this often involves a small "seed region" of only 6 to 8 nucleotides at the 5' end.

MicroRNAs and Argonaute RNA binding
MicroRNAs and Argonaute RNA binding

Once attached, the miRNA can silence the mRNA in several ways. It might cleave the mRNA strand into two pieces. It can also destabilize the mRNA by shortening its poly(A) tail. In humans and many other animals, the most common method is destabilizing the mRNA to prevent it from being translated into a protein.

MiRNA mechanisms
MiRNA mechanisms

The creation of these molecules, known as biogenesis, is a multi-step process. It usually begins with transcription by RNA polymerase II, which creates a long molecule called a pri-miRNA. This pri-miRNA contains structures that fold back on themselves to form hairpins or stem-loops.

Examples of microRNA stem-loops
Examples of microRNA stem-loops

In the cell nucleus, a protein called DGCR8 recognizes these hairpins. DGCR8 works with an enzyme called Drosha to form the microprocessor complex. This complex cuts the RNA to release a smaller piece called a pre-miRNA.

5b16 drosha dgcr8
5b16 drosha dgcr8

This pre-miRNA is then moved from the nucleus to the cytoplasm by a protein called Exportin-5. This transport process requires energy to move the molecule through the cell's gates.

3a6p xpo5 ran miRNA
3a6p xpo5 ran miRNA

Scientists have discovered that miRNAs are incredibly diverse and widespread. The human genome may encode over 1,900 different miRNAs. However, the MirGeneDB database, which is manually curated, only lists about 500 as confirmed, bona fide miRNAs. These molecules are very active in mammalian cells. They appear to target approximately 60% of all human and mammalian genes. This means a single miRNA can influence hundreds of different messenger RNAs. For example, highly conserved miRNAs in vertebrates target about 400 different mRNAs on average.

The history of miRNA research is a story of unexpected discovery. In 1993, Victor Ambros and his team discovered the first miRNA while studying the nematode *C. elegans*. They found a molecule called *lin-4* that controlled larval development. At first, many scientists thought this was just a strange quirk of worms. However, in 2000, a second small RNA called *let-7* was identified. This RNA was found to be conserved across many different species. This discovery suggested that small RNAs were a universal way to regulate development.

MiRNA-biogenesis
MiRNA-biogenesis

In 2024, Victor Ambros and Gary Ruvkun were awarded the Nobel Prize for these discoveries.

Many miRNAs are evolutionarily conserved, meaning they have remained similar across many millions of years. For instance, 90 families of miRNAs have been conserved since the common ancestor of fish and mammals. This conservation implies that these molecules perform vital biological roles. When these roles are disrupted, it can lead to health issues. For example, the first human disease linked to miRNA deregulation was chronic lymphocytic leukemia. In this condition, miRNAs can act as either tumor suppressors or oncogenes.

Because of these links, scientists are currently investigating miRNA-based therapies to treat diseases.

MicroRNAs also show remarkable complexity through processes like RNA editing. About 6% of human miRNAs undergo editing, where enzymes change specific nucleotides in the sequence. This creates "isomiRs," which are slightly different versions of the original miRNA. This editing can change how a miRNA targets genes or even stop its processing entirely. Furthermore, miRNAs can be found within the sequences of other genes, known as introns or exons. This allows the cell to regulate the miRNA and its host gene at the same time. This intricate system ensures that the right proteins are made at exactly the right moment.

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🖼️ Images & Media (8)
File:MiRNA.svg
MiRNA.svg
File:Examples of microRNA stem-loops.jpg
Examples of microRNA stem-loops.jpg
File:MiRNA-biogenesis.jpg
MiRNA-biogenesis.jpg
File:5b16 drosha dgcr8.png
5b16 drosha dgcr8.png
File:3a6p xpo5 ran miRNA.png
3a6p xpo5 ran miRNA.png
File:MicroRNAs and Argonaute RNA binding.svg
MicroRNAs and Argonaute RNA binding.svg
File:MiRNA mechanisms.jpg
MiRNA mechanisms.jpg
File:Role of miRNA in a cancer cell.svg
Role of miRNA in a cancer cell.svg
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