Page 23 - 12024 Business Dir

MEDICAL YEAR MEDICAL YEAR
MEDICAL YEAR
MEDICAL YEAR
IN REVIEW IN REVIEW
IN REVIEW
IN REVIEW

When a Micro Discovery Leads to ulate transcription but can also activate translation. We have a deeper developmental events. Genes Dev. 1987 Jun;1(4):398-414. doi:

a Nobel Prize ® understanding of the molecular mechanisms underlying this process. 4. Bhaskaran M., Mohan M. MicroRNAs: history, biogenesis, and
10.1101/gad.1.4.398
Given their vital roles in cell development and function, it is not sur-

species. For instance, let-7, which is essential for larval development in
2014 Jul;51(4):759-74. doi: 10.1177/0300985813502820
By Kreny Savaliya, Hunter Buescher and Ramaswamy Sharma, MS, PhD prising that they are evolutionarily conserved across a wide range of their evolving role in animal development and disease. Vet Pathol.
C. elegans, is also found in humans. 5. Lee R.C., Feinbaum R.L., Ambros V. “Nomination and Selection
ir Alfred Nobel, a Swedish chemist credited with inventing explo- Technology. The Horvitz laboratory used Ceanorhabditis elegans, a Dysregulation of miRNAs is associated with many pathologies. of Medicine Laureates.” NobelPrize.org, 2019. www.nobelprize.
sives such as dynamite, blasting gelatin and ballistite, bequeathed roundworm that is just a mm in length, as a model to determine how Mutations in miRNA-coding genes have been associated with con- org/nomination/medicine/
Shis vast estate for recognizing distinguished, paradigm-shifting cells develop. Horvitz, John Sulston and Martin Chalfie (all Nobel ditions such as congenital hearing loss and skeletal abnormalities. 6. The C. elegans heterochronic gene lin-4 encodes small RNAs with
achievements that benefit humans in the fields of physics, chemistry, laureates) had earlier characterized many heterochronic mutant C. ele- Therefore, miRNAs are being scrutinized as targets for drug devel- antisense complementarity to lin-14. Cell. 1993 Dec 3;75(5):843-
physiology or medicine, economic sciences, literature and peace. These gans worms, so-called because their temporal pattern of cell develop- opment as well as therapeutic agents themselves. For example, inhibi- 54. doi: 10.1016/0092-8674(93)90529-y
awards, known as Nobel Prizes, come with a diploma, a medal and a ment was disturbed by those mutations, when they worked in Sydney tors targeting miR-92a and miR-122 are under investigation for their 7. O’Brien J., Hayder H., Zayed Y., Peng C. Overview of MicroR-
cash prize of 11 million Swedish kronor, and are presented by the King Brenner’s laboratory (also a Nobel laureate); one such heterochronic potential benefits in treating cardiovascular diseases and hepatitis C, NA Biogenesis, Mechanisms of Actions, and Circulation. Front
of Sweden. Victor Ambros, a professor of molecular medicine at the mutant was lin-4 (cell lineage abnormal-4) that was unable to lay eggs respectively. Additionally, several miRNA candidates are currently Endocrinol (Lausanne). 2018 Aug 3;9:402. doi: 10.3389/
University of Massachusetts Chan Medical School, and Gary Ruvkun, and displayed defects in cell lineage. Ambros and Ruvkun further ana- being tested for targeting cancer in clinical trials. Their role as bio- fendo.2018.00402. https://doi.org/10.3389/fendo.2018.00402
a professor of genetics at Harvard Medical School, were selected this lyzed these heterochronic mutants in Horvitz’s laboratory. Ambros markers is particularly compelling as they show remarkable promise 8. “The Nobel Prize in Physiology or Medicine 2024.” NobelPrize.
year to receive the Nobel Prize in Physiology and Medicine for their discovered three more genes involved in heterochronicity – lin-14, in identifying and tracking pathologies such as cancer, cardiovas- org, 7 Oct. 2024. www.nobelprize.org/prizes/medicine/2024/
discovery of a new type of RNA that plays a major role in regulating lin-28 and lin-29. Both scientists continued working on these genes cular diseases and neurological disorders. Because miRNAs can be press-release/
gene expression. Their findings have led to the discovery of a thousand after they set up their own laboratories. detected in liquid biopsies such as blood and urine, they represent 9. Wang D. and Farhana A. “Biochemistry, RNA Structure.” PubMed,
other microRNAs and a better understanding of the tight genetic con- Ambros’s laboratory at Harvard University discovered that lin-4 a minimally invasive option for diagnosis, paving the way for easier StatPearls Publishing, 2020, www.ncbi.nlm.nih.gov/books/
trol exerted in our cells. inhibited lin-14 expression. Lin-14 expression is required for normal patient monitoring. NBK558999/
Our bodies consist of trillions of cells with the same genetic early-stage development but its reduced expression is associated with The landscape of RNA-based medicine continues to evolve with 10. Wightman B., Ha I., Ruvkun G. Posttranscriptional regulation of
makeup; yet, our neurons behave and function differently from our normal late-stage development. He cloned lin-4 and found that it gen- the identification of other non-coding RNA classes, including long the heterochronic gene lin-14 by lin-4 mediates temporal pattern
muscle cells. This is due to a process known as specialization, which erated an incredibly short RNA molecule that did not code for a protein. non-coding RNAs (IncRNAs), circular RNAs (circRNAs), and small formation in C. elegans. Cell. 1993 Dec 3;75(5):855-62. doi:
involves gene regulation. Genes are made up of specific sequences of Meanwhile, Ruvkun’s laboratory at Massachusetts General Hospital interfering RNAs (siRNAs). A notable milestone in this domain was 10.1016/0092-8674(93)90530-4
deoxyribonucleic acid (DNA); it was earlier thought that each gene determined that the lin-14 gene was transcribed to generate mRNA the FDA’s approval of Patisiran in 2018, the first siRNA-based drug
is transcribed to form a specific sequence of ribonucleic acid (RNA), at the later stages of development but did not make protein, i.e., lin-14 for treating hereditary transthyretin-mediated amyloidosis. While Kreny Savaliya is a medical student at the University of the
which, in turn, is translated to form a particular protein. Since all the inhibition was post-transcriptional. They also discovered a sequence in challenges such as off-target effects and the development of efficient Incarnate Word School of Osteopathic Medicine, Class of 2028.
cells in our body contain the same 22,300 protein-coding genes, only the 3’Untranslated Region (3’ UTR) of lin-14 RNA that was comple- delivery systems remain critical hurdles, the potential for RNA- She is passionate about pursuing a career in pediatrics to positively
those genes that are relevant towards its formation and function will mentary to lin-4 RNA. Together, Ambros and Ruvkun established that based diagnostics and treatments appears increasingly promising. No impact children’s health. She is also dedicated to participating in
be active in a given cell type; the remaining genes are “silenced.” Thus, the short RNA transcribed by the lin-4 gene bound to the lin-14 RNA wonder the Nobel committee is recognizing the pivotal discovery of mission trips to provide medical care to underserved communities and
the genes that are active in a neuron will be different from those in a and prevented its translation to protein. This was a groundbreaking dis- miRNA in medicine that has heralded a transformative shift in how broaden her understanding of global health issues.
muscle cell, thereby making it function differently from a muscle cell. covery, as Ambros and Ruvkun were the first to demonstrate that short we approach healthcare.
Prior to the seminal discovery of Ambros and Ruvkun, it was thought RNAs (called microRNA or miRNA) could regulate gene expression Hunter Buescher is a medical student at the University of the
that certain proteins, called transcription factors, attach to DNA and after DNA was transcribed to RNA. Their findings were published References: Incarnate Word School of Osteopathic Medicine, Class of 2028.
either promote or inhibit formation of proteins, thereby deciding in 1993 in back-to-back articles in the journal Cell. However, it took 1. “Alfred Nobel’s Will - Nobel Peace Prize.” Www.nobelpeaceprize. His interests include preventative medicine and community
which genes were active and were translated to synthesize proteins. seven more years and the identification of another microRNA, let7, for org, 30 Aug. 2021, www.nobelpeaceprize.org/nobel-peace-prize/ health.
During the 1980’s, Ambros and Ruvkun worked together as post- their discovery to be accepted by the scientific community. Many more history/alfred-nobel-s-will
doctoral fellows in the laboratory of Robert Horvitz, who received microRNAs have been discovered since. 2. Almeida M.I., Reis R.M., Calin G.A. MicroRNA history: discov- Ramaswamy Sharma, MS, PhD, is a Professor of Histology
the Nobel Prize in 2002 for his contribution towards the elucidation We now know that miRNAs are non-coding RNAs, typically ery, recent applications, and next frontiers. Mutat Res. 2011 Dec and Pathology at the University of the Incarnate Word School of
of programmed cell death during development. Interestingly, Ambros around 22 nucleotides long, that mostly interact with the 3’ UTR of 1;717(1-2):1-8. doi: 10.1016/j.mrfmmm.2011.03.009 Osteopathic Medicine. He is interested in delineating the multiple
had previously been mentored by David Baltimore, another Nobel target mRNAs, resulting in their degradation and thereby, translation- 3. Ambros V., Horvitz H.R. The lin-14 locus of Caenorhabditis molecular and cellular roles of melatonin in maintaining our
laureate, for his graduate research at the Massachusetts Institute of al repression. Recent discoveries indicate that miRNAs not only reg- elegans controls the time of expression of specific postembryonic quality of life. Dr. Sharma serves on the BCMS Publications Committee.

22 SAN ANTONIO MEDICINE • December 2024 Visit us at www.bcms.org 23