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活動簡介

Human telomerase biogenesis is a complex and highly regulated process, initiated by the sequential binding of various protein components to the RNA subunit hTR/TERC. This stepwise assembly acts as a quality control mechanism, ensuring that only properly assembled telomerase complexes are matured, while defective ones are targeted for degradation. Deficiencies in telomerase components, whether in the RNA subunit or associated proteins, are linked to severe degenerative diseases, underscoring the importance of understanding telomerase biogenesis to uncover the underlying causes of telomere biology disorders.

However, studying these processes in vivo is challenging due to the scarcity of endogenous telomerase precomplexes in cells, which limits the ability to characterize the molecular mechanisms. To address this, we developed in vitro cell-free systems, enabling us to dissect telomerase assembly and investigate the 3′-end processing of hTR. Through these systems, we identified LARP3, LARP7, and MePCE as novel players in the early stages of hTR biogenesis, providing new insights into the regulation of telomerase assembly.

Our result highlights how the interplay between structural features of hTR and the binding of specific proteins regulates the stability and maturation of hTR, which is essential for functional telomerase assembly and provide a valuable insight into development of therapeutics for telomere biology disorders.

This study is has been published in Nature communications (https://www.nature.com/articles/s41467-024-50422-w )