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

Zeid, Lina Y. Abou; Shanmugapriya, Shanmugapriya; Rumney, Rebecca L.; Mosser, Dick D.

doi:10.1007/s12192-021-01242-0

Cited by 5 publications

(1 citation statement)

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“…Dicer is cleaved by caspases during apoptosis triggered by TNFα and other stress stimuli ( 65 ). Multiple RNA-silencing factors (Drosha, DGCR8, Dicer, and TRBP) are cleaved by caspases in heat-shocked cells, an effect inhibited by the overexpression of HSP70 ( 66 ). In this study, Dicer cleavage was not triggered by viral infection, poly(I:C) transfection, or TNFα/CHX treatment, and the expression of full-length Dicer was unaffected by these stimuli (Figure 1 ).…”

Section: Discussionmentioning

confidence: 99%

Caspase-mediated processing of TRBP regulates apoptosis during viral infection

Shibata,

Moriizumi,

Onomoto

et al. 2024

Nucleic Acids Research

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RNA silencing is a post-transcriptional gene-silencing mechanism mediated by microRNAs (miRNAs). However, the regulatory mechanism of RNA silencing during viral infection is unclear. TAR RNA-binding protein (TRBP) is an enhancer of RNA silencing that induces miRNA maturation by interacting with the ribonuclease Dicer. TRBP interacts with a virus sensor protein, laboratory of genetics and physiology 2 (LGP2), in the early stage of viral infection of human cells. Next, it induces apoptosis by inhibiting the maturation of miRNAs, thereby upregulating the expression of apoptosis regulatory genes. In this study, we show that TRBP undergoes a functional conversion in the late stage of viral infection. Viral infection resulted in the activation of caspases that proteolytically processed TRBP into two fragments. The N-terminal fragment did not interact with Dicer but interacted with type I interferon (IFN) signaling modulators, such as protein kinase R (PKR) and LGP2, and induced ER stress. The end results were irreversible apoptosis and suppression of IFN signaling. Our results demonstrate that the processing of TRBP enhances apoptosis, reducing IFN signaling during viral infection.

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Section: Discussionmentioning

confidence: 99%