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Biology subjects

Mayank, A. K.

Publications and source records attributed to Mayank, A. K..

2 recordsLinked to original sources

EDC-3 and EDC-4 Regulate Embryonic mRNA Clearance and Biomolecular Condensate Specialization

Animal development is dictated by the selective and timely decay of mRNAs in developmental transitions, but the impact of mRNA decapping scaffold proteins in development is unknown. This study unveils the roles and interactions of the DCAP-2 decapping scaffolds EDC-3 and EDC-4 in the embryonic development of C. elegans. EDC-3 facilitates the timely removal of specific embryonic mRNAs, including cgh-1, car-1, and ifet-1 by reducing their expression, and preventing excessive accumulation of DCAP-2 condensates in somatic cells. We further uncover a novel role for EDC-3 in defining the boundaries between P-bodies, germ granules, and stress granules. Lastly, we show that EDC-4 counteracts EDC-3 and engenders the assembly of DCAP-2 with the GID (CTLH) complex, a ubiquitin ligase involved in maternal-to-zygotic transition (MZT). Our findings support a model wherein multiple RNA decay mechanisms temporally partake in the clearance of maternal and zygotic mRNAs throughout embryonic development.

molecular biology↗

SCF FBXL5 ubiquitin ligase regulates stability of von-Hippel Lindau protein and the HIF1α-dependent response to hypoxia

The canonical response to changes in cellular oxygen levels consists of the ubiquitin-dependent degradation of hypoxia-inducible transcription factors (HIFs) in a prolyl hydroxylase (PHD) and von-Hippel Lindau-ElonginB-ElonginC (VHL-ElonginBC) E3 ubiquitin ligase complex-dependent manner. This regulated degradation event is oxygen-dependent and results in activation of a transcriptional program that mediates the cellular adaptation to changes in oxygen tension. Here, we show that a distinct Cullin-RING ligase complex, SKP1-CUL1-FBXL5 (SCFFBXL5), physically associates with VHL and promotes its ubiquitin-dependent degradation during hypoxia. The regulation of VHL protein stability by FBXL5 influences HIF1 expression levels and the transcriptional activation of downstream hypoxia-responsive target genes. This work identifies a novel mechanism for VHL regulation which contributes to the HIF1-mediated cellular response to hypoxia and provides an additional layer of crosstalk between iron and oxygen homeostasis.

molecular biology↗