"Northwestern Medicine scientists have discovered how molecular "traffic controllers" in cells influence aging and cellular senescence - a state where cells stop dividing but remain metabolically active. The study, published in Molecular Cell, sheds light on the process of transcribing DNA into RNA, a critical step in gene expression, and how it is tightly regulated and connected to age-related changes."
"In the study, Shilatifard and his collaborators focused on proteins called transcription elongation factors, which help RNA polymerase II - the enzyme that uses DNA as template to make messenger RNA - move smoothly along the DNA and is important for the regulation of gene expression. Using advanced genetic tools and high-resolution RNA sequencing, they examined the role of elongation factors and identified NELF and SPT6 to be involved in cellular senescence. These proteins were found to play distinct roles in shaping which RNA variants, called isoforms, were produced."
Transcription elongation factors NELF and SPT6 regulate RNA polymerase II progression and determine which mRNA isoforms are produced. Deletion of NELF halts cell proliferation without causing cell death, producing a senescent state. Advanced genetic tools and high-resolution RNA sequencing revealed distinct roles for NELF and SPT6 in shaping senescence-associated transcriptional programs. These elongation factors directly influence patterns of transcription elongation that connect to age-related changes in gene expression. Modulation of these factors presents multiple potential therapeutic windows to alter cellular senescence and develop anti-aging interventions.
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