The 2024 Nobel Prize in Physiology or Medicine has been awarded jointly to Victor Ambros and Gary Ruvkun “for the discovery of microRNA and its role in post-transcriptional gene regulation”.
MicroRNAs (miRNAs) belong to a family of small, non-coding, single-stranded RNA molecules that are responsible for regulating gene expression in plants, animals, and some viruses. miRNAs have been extensively studied over the past two decades for their role in various cellular processes such as differentiation, metabolic homeostasis, proliferation and apoptosis.
miRNAs function by binding to either the 3’ end of messenger RNA (mRNA), thereby acting as translational repressors or by interacting with the 5’ end where they play a role in transcriptional regulation. All this happens in the cytoplasm of the cell and has direct implications on the types and amounts of proteins the cells make.
The first miRNA, Lin-4, was discovered in 1993 in the nematode Caenorhabditis elegans.
miRNAs are typically 18–25 nucleotides in length. They are derived from longer precursors, which are double-stranded RNAs called pri-miRNAs. The process of biogenesis happens in the nucleus and cytoplasm where pri-miRNAs form distinct hairpin-like structures that are recognized and cleaved by the Microprocessor, a heterodimer complex formed by DROSHA and DGCR8 that cleave pri-miRNAs to pre-miRNAs. The pre-miRNAs are then exported to the cytoplasm where they are finally processed to form miRNAs.
miRNAs play an important role in the organism’s development by regulating the genes and proteins right from the embryogenesis to the development of organ and organ systems, thus playing an indispensable role in maintaining cellular homeostasis. While intracellular miRNAs play a role in transcriptional/translation regulation, extracellular miRNAs function as chemical messengers to mediate cell-cell communication. Dysregulation of miRNAs has been implicated in various diseases such as cancer (miRNAs acting as both activators and repressor of genes), neurodegenerative disorders and cardiovascular diseases. Understanding and elucidating changes in miRNA expression profiling can lead to new biomarker discovery with concomitant new therapeutic approaches for disease prevention. miRNAs also play a critical role in the development and pathogenesis of infections caused by micro-organisms such as bacteria and viruses by regulating the genes of the immune system to mount an effective response to the disease.
The importance and role played by miRNAs warrant further investigation and research which coupled with integration of genomic, transcriptomic, and/or proteomic data, will enhance our mechanistic understanding of the cellular interactions and disease. This can lead to the development of novel miRNA based therapies by exploiting miRNA as actimirs (utilizing miRNAs as activators for replacement of miRNAs that have been mutated or deleted) and antagomirs (utilizing miRNAs as antagonists where there is abnormal upregulation of the said mRNA) for prevalent and emerging human and animal diseases.
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Refernces
- NobelPrize.org. Press release – The Nobel Prize in Physiology or Medicine 2024. Posted 7 October 2024. Available at https://www.nobelprize.org/prizes/medicine/2024/press-release/
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