Structure and Function of microRNA (miRNA)

The microRNA (miRNA) represents a fascinating class of small non-coding RNA molecules that play a pivotal role in the intricate regulatory networks governing gene expression. The microRNA (miRNA) is a short RNA sequence, typically consisting of 20-22 nucleotides and exerts influence at the post-transcriptional level.

The full form of miRNA:

The miRNAs constitute a class of small, non-coding RNA molecules that play pivotal roles in regulating gene expression. Despite their diminutive size, miRNAs exert significant influence over a multitude of biological processes. The term “miRNA” itself stands for “Micro Ribonucleic Acid,” reflecting its short nucleotide length and its classification as a type of RNA.

What is microRNA (miRNA):

The journey of miRNA begins in the nucleus, where primary miRNA transcripts are transcribed from specific genes by RNA polymerase II. These primary transcripts, known as pri-miRNAs, fold into hairpin structures. The microprocessor complex, comprising the RNase III enzyme Drosha and its cofactor DGCR8, then cleaves the pri-miRNA to yield precursor miRNAs (pre-miRNAs). Pre-miRNAs are subsequently transported to the cytoplasm by Exportin-5, where the RNase III enzyme Dicer processes them into mature miRNAs. The resulting mature miRNA is incorporated into the RNA-induced silencing complex (RISC), setting the stage for its regulatory functions.

If you want to know about siRNA then read the article: Structure and Function of small interfering RNA (siRNA).

The structure of microRNA (miRNA):

The microRNA (miRNA) are small RNA molecules with a remarkably intricate structure that belies their substantial regulatory impact on gene expression. The structure of miRNAs is a key factor in understanding their function and versatility in orchestrating various cellular processes.

At its core, a typical miRNA molecule is composed of approximately 20 to 22 nucleotides. Nucleotides are the building blocks of RNA and DNA, and in miRNAs, they form a single-stranded chain. The structure of a miRNA can be divided into specific regions, each with its own functional significance.

1. Seed Region: The seed region, typically comprising nucleotides 2-8 at the 5′ end of the miRNA, is a critical determinant of target recognition. This region serves as a guide for the miRNA to identify and bind to complementary sequences in the messenger RNA (mRNA) of target genes.
2. Mature Region: This encompasses the entire length of the miRNA and includes the seed region. The mature region is essential for the interaction with the RNA-induced silencing complex (RISC), a molecular machinery that facilitates the silencing or degradation of target mRNAs.
3. 5′ and 3′ Ends: The 5′ and 3′ ends of the miRNA play roles in stability and processing. The 5′ end often undergoes post-transcriptional modifications, while the 3′ end contributes to the precision of target recognition.
4. Hairpin Structure: Before miRNAs mature into their functional form, they are initially transcribed as long precursor molecules, known as primary miRNAs (pri-miRNAs). These pri-miRNAs fold into hairpin structures, which are then processed in the nucleus to form precursor miRNAs (pre-miRNAs), and further processed in the cytoplasm to generate the mature, functional miRNA.

If you want to know about the gene silencing then read the article: What is Gene Silencing | Types, Mechanisms, Examples and Uses.

The function of microRNA (miRNA):

Despite their small size, typically consisting of 20-22 nucleotides, microRNA (miRNA) wield significant influence over the intricate dance of genetic information, contributing to the fine-tuning of cellular functions and maintaining homeostasis.

The primary function of microRNA (miRNA) lies in their ability to modulate gene expression at the post-transcriptional level. This regulatory prowess is executed through a series of intricately choreographed steps:

1. Target Recognition: MiRNAs recognize and bind to specific messenger RNA (mRNA) molecules, guided by a complementary sequence within the miRNA, particularly in its seed region (nucleotides 2-8). This interaction occurs within the RNA-induced silencing complex (RISC), a molecular machinery that serves as the conductor of the miRNA symphony.
2. Gene Silencing: Once bound to their target mRNA, miRNAs can enact gene silencing through two main mechanisms. They can either inhibit the translation of the mRNA into protein, or they can induce the degradation of the mRNA molecule. By interfering with these crucial steps, miRNAs act as molecular brakes, modulating the expression levels of their target genes.
3. Regulation of Development and Differentiation: MiRNAs play a central role in developmental processes and cellular differentiation. They contribute to the precision and timing of developmental events by regulating the expression of genes involved in these processes. This involvement is particularly crucial during embryogenesis, where miRNAs sculpt the blueprint of an organism.
4. Response to Environmental Stimuli: Cells rely on miRNAs to swiftly adapt to changing environmental conditions and stressors. MiRNAs can be dynamically regulated in response to various signals, influencing the cellular response to stress, nutrient availability, and other external cues.
5. Disease Implications: Dysregulation of miRNAs is associated with a spectrum of diseases, including cancer, cardiovascular disorders, neurodegenerative diseases, and immune-related conditions. Some miRNAs act as oncogenes, promoting tumor growth, while others function as tumor suppressors, inhibiting uncontrolled cell proliferation.

The Biogenesis of microRNA (miRNA):

MicroRNA (miRNA) biogenesis is a highly regulated and orchestrated process that transforms genetic information into functional RNA molecules.

• The journey begins with transcription in the cell nucleus, where RNA polymerase II synthesizes primary miRNA transcripts (pri-miRNAs).
• These pri-miRNAs, often embedded in gene introns, undergo processing by the Drosha-DGCR8 complex, forming hairpin-shaped precursor miRNAs (pre-miRNAs).
• Exportin-5 transports pre-miRNAs to the cytoplasm, where Dicer, in collaboration with partner proteins, cleaves them into short double-stranded RNA duplexes.
• The mature miRNA strand is then loaded onto the miRNA-induced silencing complex (RISC). Guided by the mature miRNA, RISC identifies and binds to complementary mRNA sequences, leading to translational repression or mRNA degradation.
• This precise and sequential biogenesis pathway highlights the sophistication of miRNA regulation in fine-tuning gene expression, with implications for various cellular processes and potential therapeutic interventions.

The Pathway of microRNA (miRNA):

The pathway of microRNA (miRNA) unveils a captivating journey within the cellular landscape, where these small RNA molecules navigate a meticulously regulated course to exert profound influence over gene expression. The miRNA pathway, often referred to as the miRNA biogenesis and silencing pathway, involves a series of finely tuned steps that commence in the nucleus and culminate in the cytoplasm, shaping the cellular symphony of genetic regulation.

1. Transcription: The journey kicks off with the transcription of miRNA genes by RNA polymerase II, generating primary miRNA transcripts (pri-miRNAs). These pri-miRNAs can be independent transcriptional products or can be nested within the introns of protein-coding genes.
2. Pri-miRNA Processing: In the nucleus, the enzyme complex Drosha-DGCR8 meticulously cleaves the pri-miRNAs, creating precursor miRNAs (pre-miRNAs) characterized by hairpin structures. This intricate haircutting process defines the initial form of miRNAs.
3. Export to Cytoplasm: Transported by Exportin-5, the pre-miRNAs travel from the nucleus to the cytoplasm, marking the transition from their birthplace to the site of their functional activity.
4. Dicing and Formation of Mature miRNA: Once in the cytoplasm, the pre-miRNAs encounter Dicer, a key enzyme accompanied by partner proteins. Dicer cleaves the pre-miRNAs into short double-stranded RNA duplexes. From this duplex, the mature miRNA strand is chosen to guide the miRNA-induced silencing complex (RISC).
5. Loading onto RISC: The mature miRNA is loaded onto the RISC, a versatile molecular machine that acts as the executioner of miRNA function. The RISC, guided by the mature miRNA, embarks on a quest to find specific mRNA targets based on sequence complementarity.
6. Target Binding and Regulation: The RISC identifies mRNA targets with complementary sequences to the mature miRNA. Once identified, the RISC either represses translation or induces degradation of the targeted mRNA, ultimately fine-tuning gene expression and influencing diverse cellular processes.

The microRNA (miRNA) Mediated Gene Silencing:

The microRNA (miRNA) mediated gene silencing is a sophisticated cellular process crucial for the fine-tuning of gene expression. The journey begins with the transcription of miRNA genes, generating primary miRNA transcripts (pri-miRNAs). These pri-miRNAs are processed in the nucleus by the Drosha-DGCR8 complex, yielding precursor miRNAs (pre-miRNAs) with characteristic hairpin structures. Transported to the cytoplasm, pre-miRNAs encounter Dicer, which cleaves them into mature miRNA duplexes. The mature miRNA strand is then loaded onto the miRNA-induced silencing complex (RISC), guiding RISC to target specific mRNA sequences.

In this exploration of microRNA (miRNA), we delve into their biogenesis, mechanisms of action, and the intricate web of interactions that govern their function. As we navigate this intricate landscape, the significance of miRNAs in shaping cellular dynamics becomes increasingly evident, underscoring their potential as diagnostic markers and therapeutic targets.