Caspase-mediated cleavage of miRNA processing proteins Drosha, DGCR8, Dicer, and TRBP2 in heat-shocked cells and its inhibition by HSP70 overexpression.

Autor: Abou Zeid LY; Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, N1G 2W1, Canada., Shanmugapriya S; Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, N1G 2W1, Canada., Rumney RL; Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, N1G 2W1, Canada., Mosser DD; Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, N1G 2W1, Canada. rmosser@uoguelph.ca.
Jazyk: angličtina
Zdroj: Cell stress & chaperones [Cell Stress Chaperones] 2022 Jan; Vol. 27 (1), pp. 11-25. Date of Electronic Publication: 2021 Oct 31.
DOI: 10.1007/s12192-021-01242-0
Abstrakt: Cells respond to stress through adaptive mechanisms that limit cellular damage and prevent cell death. MicroRNAs act as regulators of stress responses and stress can impact the functioning of miRNA biogenesis pathways. We were interested in the effect that severe proteotoxic stress capable of inducing apoptosis may have on miRNA biogenesis and the impact of the molecular chaperone protein HSP70 under these conditions. We found that the miRNA processing enzymes Drosha and Dicer and their accessory proteins DGCR8 and TRBP2 are cleaved by caspases in apoptotic cells. Overexpression of HSP70 prevented caspase activation and the degradation of these processing proteins. Caspase cleavage of TRBP2 was mapped to amino acid 234 which separates the two dsRNA-binding domains from the C-terminal Dicer interacting domain. Overexpression of TRBP2 was found to increase miRNA maturation, while expression of either of the fragments generated by caspase cleavage impaired maturation. These results indicate that inactivation of miRNA biogenesis is a critical feature of apoptosis and that cleavage of TRBP2, rather than simply a loss of function, serves to create positive acting inhibitors of pre-miRNA maturation.
(© 2021. Cell Stress Society International.)
Databáze: MEDLINE
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