miRNAs

What are miRNAs?

MicroRNAs (miRNAs) are molecules of non-coding RNA around 22 nucleotides long and widely distributed in animals, plants, viruses and microorganisms. They regulate post-transcriptional gene expression by interacting with the 3' untranslated region (3'UTR) of the target mRNA, and impact many aspects of cell biology, from development to differentiation to apoptosis and disease generation.

What is the mechanism of action of miRNAs?

The miRNA action has two main steps:

A. Translation inhibition: when the miRNA is not fully complementary to the target mRNA, the miRNA binds to the 3'UTR region of the target mRNA, thus preventing the ribosome from recognizing and binding to the target mRNA, leading to inhibition of protein translation. This mechanism is more common in mammals.

B. mRNA degradation: When the miRNA is perfectly or nearly perfectly complementary to the target mRNA, then the miRNA cleaves the target mRNA via RISC (RNA-induced silencing complex) cleavage, and the target mRNA will then be degraded. This usually happens because the AGO2 protein is an endonuclease that breaks down the target mRNA.

Figure 1. miRNA biosynthesis and its mechanism of action^[1].

Biosynthesis of miRNAs

It is multistep in how miRNAs are produced: primary miRNAs (pri-miRNAs) are first transcribed by RNA polymerase II, broken down into precursor miRNAs (pre-miRNAs) by the enzyme Droshazyme, and finally broken down again by the enzyme Dicer to produce a mature, double-stranded miRNA. Lastly, the mature miRNAs bind to the Argonaute protein and form an RNA-induced silencing complex (RISC) that then silences the target mRNA.

Major Properties and Functions of miRNAs

• Gene Expression Regulation

MiRNAs work by cleaving complementary sequences to messenger RNA (mRNA), inhibiting translation, or breaking down mRNA. This accurate process allows gene networks responsible for growth, development, and disease to be precisely tuned.

• Role in Development and Disease

MiRNAs are crucial in developmental biology to ensure correct tissue patterning and cell fate decisions. MiRNA expression deregulation is associated with cancer, cardiovascular disease, and neurodegenerative diseases – the most common targets for therapeutic intervention.

• Conservation Across Species

It is also a sign of the evolutionary importance of miRNA sequences being conserved. This universality allows cross-species research, making our observations about basic biological processes more useful.

Using miRNAs to treat cancer: How it works

• MiRNAs regulate gene expression at the post-transcriptional level by binding to the 3' non-coding region of target gene mRNAs, inhibiting their translation or promoting their degradation. It is through this process that miRNAs can directly influence a range of cellular physiological functions such as cell proliferation, apoptosis, differentiation, and metabolism.
• MiRNAs can also be involved in cancer development as tumor suppressors or oncogenes. For instance, miR-34a suppresses the growth of tumors through apoptosis, while miR-21 promotes gastrointestinal tumour growth. If activated and/or inactivated miRNAs that act as oncogenes, cell division becomes out of balance and tumors grow, which can cause cancer.
• MiRNAs regulate several signalling networks and protein targets that play a role in cancer genesis and progression. For instance, miRNAs can control cell cycle, apoptosis, angiogenesis, and metastasis.
• MiRNAs are also involved in remodeling the tumour immune microenvironment, which in turn influences how immune cells and other molecules of the tumor microenvironment, including tumor necrosis factor-alpha (TNF-α) and tumor necrosis factor receptor (TNFR), operate.
• MiRNAs interact with RBPs to modulate mRNA stability, transport, and degradation for cellular homeostasis. This feedback loop can regulate mRNA transcription and degradation of target proteins, which in turn controls the development of cancer.
• The biogenesis of miRNAs is also controlled by multiple processes, such as amplification, deletion, mutation, and epigenetic silencing. These interactions influence the levels and activity of miRNAs and, therefore, the growth and progression of cancer.
• MiRNAs interact with RNA-binding proteins (RBPs) to influence mRNA stabilization, transport, and degradation to maintain cellular homeostasis. This interaction can control mRNA transcription and target protein degradation, thereby regulating cancer progression.
• The biogenesis of miRNAs is also regulated by a variety of mechanisms, including amplification, deletion, mutation, and epigenetic silencing. These processes affect the expression and function of miRNAs, which in turn influence cancer development and progression.

Figure 1. miRNA-based anticancer therapeutic strategies^[1].

miRNAs Development Services at Alfa Chemistry

Alfa Chemistry provides therapeutic miRNA development. We are your miRNA research and applications partner. From basic discovery to drug discovery, our services allow scientists to take advantage of miRNA biology.

• Target selection.
• Sequence design of miRNAs.
• Synthesis and chemical modification of miRNAs.
• Purification and analysis of miRNAs.
• Delivery system selection or development of miRNAs.
• Nonclinical evaluation of miRNAs.
• Scale-up of miRNAs.

And no matter where you are at in miRNA evolution, we can help.

Our products and services are for research use only and cannot be used for any clinical purposes.

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