Publications by authors named "K Timcheva"

Here, we present a detailed protocol to study the role of a human nuclear m6A RNA reader, YTHDC1, on chromatin-associated RNA targets. We describe steps for RNA extraction coupled to subnuclear fractionation to identify and study RNA-based regulations that take place in the chromatin-associated fraction. We then detail an RNA immunoprecipitation procedure adapted to identify chromatin-associated RNA targets.

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Background: One-third of cancers activate endogenous synthesis of serine/glycine, and can become addicted to this pathway to sustain proliferation and survival. Mechanisms driving this metabolic rewiring remain largely unknown.

Methods: NKX2-1 overexpressing and NKX2-1 knockdown/knockout T-cell leukaemia and lung cancer cell line models were established to study metabolic rewiring using ChIP-qPCR, immunoblotting, mass spectrometry, and proliferation and invasion assays.

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Article Synopsis
  • Heat stress triggers significant changes in gene expression, primarily involving the protein YTHDC1, which interacts with N-methyladenosine (mA) RNA modifications.
  • YTHDC1 relocates within the genome during heat stress, enhancing the expression of heat shock proteins (HSPs) and leading to altered transcript processing for many genes.
  • The study suggests that YTHDC1's accumulation in specific nuclear stress bodies helps regulate and time the overall gene expression response to heat stress.
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In eukaryotes, the heat shock response is orchestrated by a transcription factor named Heat Shock Factor 1 (HSF1). HSF1 is mostly characterized for its role in activating the expression of a repertoire of protein-coding genes, including the heat shock protein (HSP) genes. Remarkably, a growing set of reports indicate that, upon heat shock, HSF1 also targets various non-coding regions of the genome.

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