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bioRxiv · 10.1101/2022.10.12.509557

Essential role of the amino-terminal region of Drosha for the Microprocessor function

Hata, A.·Prabhakar, A.·Jiang, X.·Hu, S.·Tang, J.·Ghatpande, P.·Lagna, G.
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Abstract

The ribonuclease (RNase) III enzyme Drosha enables processing of microRNA (miRNA) primary transcripts (pri-miRNAs) and control of ribosomal protein (RP) biogenesis by the Microprocessor. The extensively studied carboxyl-terminal half of Drosha is sufficient to crop pri-miRNAs in vitro, but the function of the evolutionarily conserved Drosha amino-terminal region (NTR) is unknown, despite it harboring mutations linked to a hereditary vascular disorder. Here, we provide evidence that, when replacing the endogenous Drosha, a mutant missing the NTR ({Delta}N-Drosha) fails to associate with endogenous pri-miRNAs and to support the expression of all miRNAs, except the miR-183 cluster. Surprisingly, Argonaute2 (Ago2) associates with and cleaves pri-miR-183 in {Delta}N-Drosha cells and in Drosha-depleted cells. {Delta}N-Drosha is also unable to inhibit RP biogenesis upon serum starvation. Thus, Drosha NTR is essential for pri-miRNA processing and RP biogenesis in vivo, and Ago2 can process the miR-183 cluster in the absence of Drosha.

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Hata, A., Prabhakar, A., Jiang, X., Hu, S., Tang, J., Ghatpande, P., Lagna, G.. 2022-10-13. Essential role of the amino-terminal region of Drosha for the Microprocessor function. https://doi.org/10.1101/2022.10.12.509557

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