Splicing Solutions The central dogma of biology describes how DNA serves as the instruction book for life, where a sequence of DNA is transcribed into messenger RNA, which is then translated into a protein. However, the process is more complex than it appears. Many steps influence both transcription and translation. One important step is RNA splicing. During splicing, certain parts of the RNA that don’t carry instructions for building proteins (introns) are removed. The remaining parts(exons) are joined together. Alternative splicing allows different combina- tions of exons to create multiple messenger RNA (mRNA) transcripts from a single gene, ultimately producing various proteins. Scientists have uncovered naturally occurring, highly conserved alternative exons known as poison exons. These exons contain genetic code that prematurely stops the production of proteins. When these are present within a gene, these exons trigger a process called nonsense- mediated decay, reducing overall protein production. Recent research into alternative splicing in the brain has identified numerous transcripts containing poison exons, some of which are linked to neurodevelopmental disorders.
Transparent Mice The familiar orange tint on your fingers after munching on Doritos® comes from Tartrazine, also known as Yellow No. 5, an artificial dye. Recently, researchers found that this same dye can
temporarily make the skin of live mice transparent, exposing their blood vessels, muscles, and organs. Normally, skin is opaque because it's made up of water, lipids, proteins, and other cellular components. These components bend light in different ways, causing light to scatter in all directions, which makes the skin look solid. Researchers aimed to find a light-absorbing molecule that could reduce this scattering and enhance skin transpar- ency. After studying 21 different synthetic dyes, they found that Yellow No. 5 increases refraction for red and yellow light and absorbs blue and ultraviolet light. When the dye is applied to the skin, it enhances the light transmission through the skin by suppressing its ability to scatter light, creating transparency.
These exons contain genetic code that prematurely stops the production of proteins
In experiments, the dye was applied to the skin of mice, and within 10 minutes, the underlying tissues became visible. When rubbed onto the abdomen, the dye revealed the digestive tract in action under visible light, and when spread onto
Dravet syndrome, a rare genetic disorder that causes severe epilepsy beginning in early childhood, is an example of a condition impacted by poison exons. Over 80% of patients have only one working copy of the SCN1A gene, which encodes a sodium channel protein crucial for neurotransmission. The other, non-working copy of the SCN1A gene is usually caused by the inclusion of a poison exon in the mRNA transcript. A new drug, STK-001, prevents the inclusion of the poison exon and boosts the protein's production. In mice, this treatment increased healthy protein levels six-fold initially, stabiliz- ing at a two-fold increase. Early human trials have shown a dramatic reduction in seizure frequency. These early trial results and other potential therapies involving poison exons highlight a promising new direction in genetic medicine. n REFERENCE: Sheridan, C., et al., A new class of mRNA drugs targets poison exons. Nature Biotechnology [2024] 42: 1159–1161 https://doi.org/10.1038/s41587-024-02355-4
the leg, it exposed the muscles. High-resolution laser imaging showed detailed views of nerves in the digestive system and the brain’s blood vessels. This transparency effect lasted 10–20 minutes, with no adverse effects observed in the mice. Although Yellow No. 5 is an FDA-approved food additive, its use on human skin remains untested. Human skin is thicker than that of mice, so further research is needed to determine the appropriate amount of dye and absorption time for safe human use. This dye could have several human applications, including making blood draws easier, improving CT imaging, aiding early skin cancer detection, and even helping with laser-based tattoo removal. n REFERENCE: Ou, Z., et al., Achieving optical transparency in live animals with absorbing molecules. Science [2024] 385, eadm6869. https://doi.org/10.1126/science.adm6869
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