Project description:Mitochondrial translation was investigated by mitochondrial ribosome profiling (mitoRiboSeq) in three HEK293 cell lines: HEK293 wildtype, mtRF1 knockout 1, and mtRF1 knockout 2
Project description:The function of the mitochondrial release factors mtRF1 and mtRF1a was investigated by mitochondrial ribosome profiling (mitoRiboSeq) in Flp-In T-Rex human embryonic kidney 293 (HEK293) and mouse neuroblastoma Neuro-2a (N2a) cell lines.
Project description:Small RNA sequencing was used to examine RNA degradation products in mitochondria from mice lacking the nuclease subunit of the mitochondrial RNase P (MRPP3).
Project description:The mitochondrial genome encodes 13 well-characterized mRNAs but, similar to the nuclear genome, it has the potential to encode many additional proteins through previously unannotated open reading frames. Using MitoRiboSeq, we detected dozens of new mitochondrial-derived microproteins in both cell lines and liver tissues. We demonstrate that MOTS-c, a previously described microprotein, shows a significant decrease during senescence induction, and its supplementation is sufficient to prevent key cellular dysfunctions associated with this process. This work significantly deepens our understanding of the mitochondrial genome and underscores its relevance for functional and therapeutic discoveries.
Project description:Shank2 is an excitatory postsynaptic scaffolding protein strongly implicated in autism spectrum disorders (ASD). Shank2-mutant mice with a homozygous deletion of exons 6 and 7 show decreased NMDA receptor (NMDAR) functions and autistic-like behaviors in juvenile (~postnatal day or P21) and adult (> P56) stages that are rescued by NMDAR activation. These mice, however, show an opposite change increased NMDAR functions—at ~P14, and NMDAR suppression by early and chronic memantine treatment during P7–21 prevents NMDAR hypofunction and autistic-like behaviors at juvenile (~P21) and adult (~P56) stages. To explore molecular mechanisms underlying the long-lasting effects of early memantine treatment, we performed RNA-Seq analysis of forebrains from wild-type and Shank2-mutant mice early and chronically treated with vehicle or memantine. Memantine-treated Shank2-mutant mice showed upregulations of chromatin-related genes and downregulations of mitochondria- and ribosome-related genes. In addition, vehicle-treated Shank2-mutant mice showed transcriptomic patterns that are largely opposite to those observed in ASD, as supported by the expression patterns of ASD-risk/related genes and cell-type-specific genes. These patterns, likely representing compensatory changes, were weakened by early memantine treatment. These results suggest that early chronic memantine treatment in Shank2-mutant mice alters chromatin- and mitochondria/ribosome-related gene expressions and weakens anti-ASD transcriptomic patterns.