Biology subjects

Chugunova, A.

Publications and source records attributed to Chugunova, A..

3 recordsLinked to original sources

bioRxiv2024

Increase in ER-mitochondria contacts and mitochondrial fusion are hallmarks of mitochondrial activation during embryogenesis

Mitochondrial ATP production is essential for development, yet the mechanisms underlying the continuous increase in mitochondrial activity during embryogenesis remain elusive. Using zebrafish as a model system for vertebrate development, we comprehensively profile mitochondrial activity, morphology, metabolome, proteome and phospho-proteome as well as respiratory chain enzymatic activity. Our data show that the increase in mitochondrial activity during embryogenesis does not require mitochondrial biogenesis, is not limited by metabolic substrates at early stages, and occurs without an increase in the abundance of respiratory chain complexes or their in vitro activity. Our analyses pinpoint a previously unexplored increase in mitochondrial-ER association during early stages in combination with changes in mitochondrial morphology at later stages as possible contributors to the rise in mitochondrial activity during embryogenesis. Overall, our systematic profiling of the molecular and morphological changes to mitochondria during embryogenesis provides a valuable resource for further studying mitochondrial function during embryogenesis.

developmental biology↗

bioRxiv2024

tRNA expression and modification landscapes, and their dynamics during zebrafish embryo development

tRNA genes exist in multiple copies in the genome of all organisms across the three domains of life. Besides the sequence differences across tRNA copies, extensive post-transcriptional modification adds a further layer to tRNA diversification. Whilst the crucial role of tRNAs as adapter molecules in protein translation is well established, whether all tRNA are actually expressed, and whether the differences across isodecoders play any regulatory role is only recently being uncovered. Here we built upon recent developments in the use of NGS-based methods for RNA modification detection and developed tRAM-seq, an experimental protocol and in silico analysis pipeline to investigate tRNA expression and modification. Using tRAM-seq we analysed the full ensemble of nucleo-cytoplasmic and mitochondrial tRNAs during embryonic development of the model vertebrate zebrafish. We show that the repertoire of tRNAs changes during development, with an apparent major switch in tRNA isodecoder expression and modification profile taking place around the start of gastrulation. Taken together, our findings suggest the existence of a general reprogramming of the expressed tRNA pool, possibly gearing the translational machinery for distinct stages of the delicate and crucial process of embryo development.

molecular biology↗

bioRxiv2020

NMD is required for timely cell fate transitions by fine-tuning gene expression and controlling translation

Cell fate transitions depend on balanced rewiring of transcription and translation programmes to mediate ordered developmental progression. Here we identify a feedback loop between nonsense-mediated mRNA decay (NMD) and translation initiation. We show that NMD controls the translation initiation factor Eif4a2 and its premature termination codon encoding isoform (Eif4a2PTC). NMD deficiency leads to translation of a specific truncated Eif4a2 protein, which elicits increased translation rates and is causative for significant delays in mouse embryonic stem cell (ESC) differentiation. Our results show identical mRNA targets for Smg5, Smg6 and Smg7, but illustrate a clear hierarchy between KOs in amplitude of target deregulation and differentiation phenotype (Smg5 > Smg6 > Smg7). This hierarchy highlights heterodimer independent functions for Smg5 and Smg7. Together, our findings expose an intricate link between mRNA stability and translation initiation control, that must be maintained for normal dynamics of cell state transitions.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cell biology↗