LARP3, LARP7, and MePCE are involved in the early stage of human telomerase RNA biogenesis

Tsai-Ling Kao, Yu-Cheng Huang, Yi-Hsuan Chen, Peter Baumann and Chi-Kang Tseng ()
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Tsai-Ling Kao: National Taiwan University
Yu-Cheng Huang: National Taiwan University
Yi-Hsuan Chen: National Taiwan University
Peter Baumann: Johannes Gutenberg University
Chi-Kang Tseng: National Taiwan University

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Human telomerase assembly is a highly dynamic process. Using biochemical approaches, we find that LARP3 and LARP7/MePCE are involved in the early stage of human telomerase RNA (hTR) and that their binding to RNA is destabilized when the mature form is produced. LARP3 plays a negative role in preventing the processing of the 3′-extended long (exL) form and the binding of LARP7 and MePCE. Interestingly, the tertiary structure of the exL form prevents LARP3 binding and facilitates hTR biogenesis. Furthermore, low levels of LARP3 promote hTR maturation, increase telomerase activity, and elongate telomeres. LARP7 and MePCE depletion inhibits the conversion of the 3′-extended short (exS) form into mature hTR and the cytoplasmic accumulation of hTR, resulting in telomere shortening. Taken together our data suggest that LARP3 and LARP7/MePCE mediate the processing of hTR precursors and regulate the production of functional telomerase.

Date: 2024
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DOI: 10.1038/s41467-024-50422-w

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