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As the air continues to dry and temperatures drop, the yearly battle against dry hands and skin has officially begun. New research from Northwestern University has discovered new evidence deep within the skin about the mechanisms controlling skin renewal and repair.
Skin’s barrier function gives it the unique ability to fight winter woes and keep water for our bodies. The outer layer of the skin, the skin, is constantly turning over to replace damaged or dead cells, creating new cells to reinforce the barrier function and heal damage. The gene regulatory mechanisms that control epidermis turnover remain incompletely understood.
“Every month we’re covered with a new layer of the epidermis,” said Northwestern’s Xiaomin Bao, who headed the study. “The next question is what does that procedure involve?”
The newspaper will be published on Jan. 19 in the journal Nature Communications.
Genetic’junk’ The scientific community has developed a wide breadth of knowledge about proteins, the workhorses of various cellular activities. Many mysteries remain about the nature of introns, non-coding segments of DNA that make up 24% of the human genome.
Regardless of the general belief that introns are nothing but”genetic junk,” they actually play critical roles in modulating RNA transcription throughout a tissue’s lifespan. RNA transcription is the first step of gene expression, in which the data from DNA is copied into RNA, which is then subsequently used as a template for synthesizing proteins to drive the specific function of a cell.
Based on where transcription terminates — within an intron or at the conclusion of a gene — an epidermal stem cell will either remain a stem cell or become a specified cell barrier function. Bao said while it’s well-known that transcription ends at the end of a gene, her lab’s research found conflicting data.
Future research could have implications for carcinoma research.
Technology critical to the discovery of the phenomenon Skin cells are gaining popularity with researchers in part because of their regenerative properties and readiness to grow in cultures. This allows researchers to apply an assortment of state-of-the-art technologies. By growing skin cells and regenerating skin tissue in a petri dish, the Bao Lab can experiment with this fast-growing tissue to determine molecular mechanisms and regulatory elements within DNA.
“Technology development is an integral driver that enabled us to uncover this new phenomenon,” Bao said.
The group used a novel genomic technique that maps where transcription stops. The integration of proteomic approaches identified RNA-binding proteins which read specific regulatory sequences in the introns.
The team further leveraged CRISPR technologies to delete genomic sequences in the intron, which provided direct evidence demonstrating that the crucial roles of introns in modulating gene expression.
Before this study, mechanisms between introns to govern the switch between a skin stem cell and a terminally differential state (for example, a cell that participates in forming a skin barrier), were unknown. Most studies ignored introns, despite them accounting for 10 to 20 times more sequences than the protein-coding regions (exons) in the human genome.
The study demonstrates that different genes may involve different sets of RNA-binding proteins to recognize the regulatory sequences in their introns. These RNA-binding proteins help to mature RNA”decide” whether to cut transcription early or dismiss termination sites within an intron during differentiation due to changes in protein availability.
“We are only starting to appreciate the roles of the intron in human health and diseases,” Bao said.
Results of this study could have broader impacts because, according to Bao, the procedures regulating skin cells are almost definitely not restricted to skin cells. Future research on other systems, including other epithelial tissues, will likely uncover similar patterns.
“We are extremely hopeful that what we’ve found is the first step to knowing what we have ignored in the past,” Bao said. My students also wish to know more about the RNA binding proteins which provide specificity in governing which site to use to terminate transcription.”