SHORT COMMUNICATION

MicroRNA: Biogenesis, significance and therapeutic benefits

Harshini Sarojini

Hiram C Polk Jr. MD, Department of Surgery, University of Louisville, Louisville, USA

Corresponding Author: Harshini Sarojini, E-mail: Harshini.Sarojini@louisville.edu

Journal of Experimental Biology and Zoological Studies. 1(2): p 119-121, Jul-Dec 2025

Received: 31/05/2025; Revised: 16/06/2025; Accepted: 19/06/2025; Published: 01/07/2025

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Abstract

MicroRNAs (miRNAs) are an abundant class of endogenous, evolutionarily conserved small non-

coding RNAs approximately 22 nucleotides in length that regulate gene expression post-

transcriptionally by the degradation and translation of target messenger RNAs. The small miRNA

molecules play an important role in cell growth, differentiation, proliferation, and apoptosis. Up to 30%

of all human genes are probably regulated by miRNAs, and each miRNA may control hundreds of gene

targets. However, only a few target genes have been confirmed for a particular miRNA.

Keywords: MicroRNA, gene expression, diagnostic marker, microRNA-based therapies.

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Introduction

In 1990s, Ambros and Ruvkun groups discovered the prototypic microRNA (miRNA) gene lin-4 in

Caenorhabditis elegans. This small molecule RNA was initially considered to be 'junk RNA' because

miRNA function has not been clarified. [1,2] In 2006, Andrew Z. Fire and Craig C. Mello won the Nobel

Prize in Medicine for their work in elucidating how miRNA regulates gene expression. Compared with

the regulators of gene expression found previously, miRNAs are different in production and

biosynthesis. The process of the miRNA biosynthesis is complicated.[3] MicroRNA genes encode long

primary miRNA transcripts, which then are processed into precursor miRNAs (pre-miRNA) by RNA

polymerase II.[4] The primary miRNA transcript possesses a 5'cap and 3'poly (A) tail. There are also

miRNAs transcribed by RNA polymerase III. Two kinds of RNAse III, Drosha and Dicer, complete the

conversion and modification of the miRNAs, respectively, in the nucleus and cytoplasm.[5] The pre-

miRNAs are exported to the cytoplasm by Exportin-5 in a RAS-related nuclear protein–guanosine

triphosphate (RAN–GTP)-dependent manner. They have a stem and loop structure. The stem represents

the RNA duplex segment. The miRNAs are cleaved by the RNAse III called Dicer at sites close to the

loop. In the cytoplasm, the pre-miRNA is sheared into a 22-nt double-stranded miRNA by Dicer. One

strand (the 'passenger' strand) is degraded, while the other strand (the 'guide' strand) enters the RNA-

induced silencing complex (RISC). The RISC targets 3' untranslated region of specific messenger RNAs

(mRNAs), destabilizing the target mRNA(s) or repressing its translation. The latter mechanism serves

as the principal pathway in animal cells.

Regulation of gene expression by miRNA

Heritable changes in gene expression that do not involve coding sequence modifications are referred to

as 'epigenetic'. Recently, gene regulation by small non-coding RNA is also considered an epigenetic

mechanism. Some specific miRNA can target specific mRNA, silencing it or inhibiting its translation.

This observation suggests novel ways to modify gene expression. MicroRNAs can also be used as an

alternative to avoid the complex gene knockout techniques (in which the function of the gene is

ascertained in its absence), and it may greatly facilitate functional genomics research. Compared with

other mechanisms of the regulation of gene expression, such as chromatin modification and

transcriptional regulation, miRNA-mediated gene regulation occurs directly before protein synthesis

and may be more suitable for fine-tuning of gene expression or quantitative regulation.

MicroRNAs as diagnostic markers and therapeutic targets

MicroRNA screens in healthy and affected tissues have started to reveal the detection and role of

miRNAs in different diseases, and aberrant miRNA expression has been discovered in many affected

tissues. Various methods, including miRNA microarray techniques, fluorescence activated cell sorting

(FACS) using fluorescent nanoparticle miRNA probes, quantification using locked nucleic acids

(LNAs), and quantitative reverse transcription-polymerase chain reaction, have been used for the

screening of miRNA expression patterns. Northern blot analysis and in situ hybridization were also

considered sensitive methods. A novel miRNA quantification method has been developed using stem–

loop RT, followed by TaqMan PCR analysis. This method enables speedy, accurate and sensitive

miRNA expression profiling and can identify and monitor potential biomarkers specific to tissues or

diseases. Gene deregulation is characteristic of a variety of diseases, particularly of cancer. There has

been an explosive increase in our understanding of the role of miRNAs in normal gene regulation and

in human disease. Expression levels of miRNA could be used as a new diagnostic marker. The

pathogenesis of numerous human diseases including aging,[6] heart diseases,[7] cancer,[8] and

autoimmune diseases,[9] has been linked to the abnormal expression of various genes potentially

regulated by miRNAs. Control of miRNA levels might also have therapeutic benefits.

Conclusion

MicroRNAs are small, non-coding RNA molecules that regulate gene expression and influence critical

biological processes such as cell growth, differentiation, apoptosis, and immune responses. They play

significant roles in the pathogenesis of various diseases, including cancer, cardiovascular conditions,

and inflammatory disorders. Due to their stability in body fluids and tissue-specific expression patterns,

miRNAs serve as valuable biomarkers for non-invasive disease diagnosis, monitoring, and prognosis.

In cancer, miRNAs may function as either tumor suppressors or oncogenes. Therapeutic strategies

targeting miRNAs such as miRNA mimics and antagomirs are being developed to modulate gene

expression. MicroRNA mimics are synthetic molecules designed to restore the function of

downregulated endogenous miRNAs, while antagomirs are complementary sequences that inhibit

specific miRNAs. Additionally, miRNAs are key regulators of inflammation and autoimmunity,

capable of exerting both pro-inflammatory and anti-inflammatory effects by modulating immune cell

function and inflammatory signaling pathways.

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