Unveiling the Non-Transcriptional Role of Transcription Factor: NCKU Team Sheds Light on a New Perspective in miRNA Regulation
Written by Jie-Ning Li. Image credit to NCKU News Center.
This year’s Nobel Prize in Physiology or Medicine was awarded to scientists who discovered microRNA (miRNA), underscoring its significance. A team led by Dr. Pai-Sheng Chen from the Department of Medical Laboratory Science and Biotechnology at National Cheng Kung University (NCKU) has identified a groundbreaking mechanism: how hypoxia-inducible factor-1 alpha (HIF-1α) dynamically regulates miRNA maturation at a non-transcriptional level. This finding solves a key upstream mystery and has been published in the prestigious journal Nucleic Acids Research, garnering global attention.A transcription-independent role for HIF-1α in modulating microprocessor assembly
A team led by Dr. Pai-Sheng Chen（left 1）from the Department of Medical Laboratory Science and Biotechnology at National Cheng Kung University (NCKU)，Dr. Jie-Ning Li（right 3）, the first author and a postdoctoral researcher who has persevered for years.
Dr. Chen attributes this remarkable achievement to the dedication of his team, particularly Dr. Jie-Ning Li, the first author and a postdoctoral researcher who has persevered for years. Other contributors include Dr. Jhen-Wei Ruan, assistant Yu-Jhen Lyu, and Ph.D. student Yi-Hsiu Weng, all of whom were trained at NCKU’s Institute of Basic Medical Sciences, the Department of Medical Laboratory Science and Biotechnology, and the Institute of Microbiology and Immunology.
Dr. Li shared that molecular biology research often requires imagining and exploring the unseen. This project spanned eight years, marked by countless failures and challenges. It was the team’s collective encouragement and passion that enabled them to persist.
Dr. Chen explained that molecular biology’s “central dogma” outlines the flow of genetic information: DNA is transcribed into coding RNA (mRNA), which is then translated into proteins to perform cellular functions. Historically, RNA was considered merely a messenger, leading to its functional roles being overlooked until the 1990s. Interestingly, scientists discovered that miRNAs, though short and non-coding, play a pivotal role in regulating gene expression by specifically binding to target mRNA. This demonstrated that RNA is more than a messenger—it has a direct role in gene regulation.
A team led by Dr. Pai-Sheng Chen has identified a groundbreaking mechanism: how hypoxia-inducible factor-1 alpha (HIF-1α) dynamically regulates miRNA maturation at a non-transcriptional level.
Dr. Li highlighted that HIF-1α is a critical transcription factor in tumor progression, enabling cancer cells to adapt to hypoxic conditions by regulating genes involved in metabolism and angiogenesis. While miRNA biogenesis abnormalities are well-documented in cancer, the mechanisms remained unclear. Through meticulous research, the team unveiled that HIF-1α inhibits miRNA maturation by interacting with DGCR8, a protein essential for miRNA biogenesis. This interaction prevents DGCR8 dimerization, disrupting the nuclear assembly of the Drosha-DGCR8 microprocessor complex and subsequently affecting primary miRNA maturation.
Dr. Li noted that this novel mechanism is not limited to cancer microenvironments under hypoxia or growth factor stimulation but is also observed in other human cells and model organisms like C. elegans and Drosophila. This suggests a widespread biological regulatory mechanism.
Dr. Pai-Sheng Chen from the Department of Medical Laboratory Science and Biotechnology at National Cheng Kung University (NCKU)
Dr. Chen highlighted the historical importance of RNA-related discoveries in Nobel Prize history, including the 2006 award for RNA interference and this year’s recognition of miRNA’s regulatory role.
NCKU’s study, published in a journal ranked in the top 2% globally, exemplifies excellence despite limited resources. The findings bridge a critical gap in understanding miRNA biogenesis abnormalities in cancer and lay the groundwork for innovative miRNA-based therapeutic strategies.
The team expressed gratitude for the support of Taiwan’s National Science and Technology Council and NCKU’s advanced facilities. Most importantly, they acknowledged the relentless efforts and perseverance of all lab members.
This finding solves a key upstream mystery and has been published in the prestigious journal Nucleic Acids Research, garnering global attention.
Provider:
NCKU News Center
Date:
2024-12-02
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