Laboratory of molecular oncology

All publications (show selected)

Loading...

Olga Doncova

Transcription factor Foxp1 plays important role in Treg

Regulatory T cells (Treg) is subpopulation of T helper lymphocytes which possesses immune suppressive properties. Treg are critical in protection from excessive immune response and autoimmunity. Unique functions of Treg are defined by transcription factor Fop3 that controls Treg-specific expression of genes. Dr. Yury Rubtsov from the Dept. of functioning of living systems in cooperation with colleagues from the Memorial Sloan-Kettering Cancer Center (New York City) studied a role of Foxp3-related protein, Foxp1, specifically in the murine Treg. In the absence of Foxp1, Treg displayed distorted Foxp3 chromatin binding which led to decreased sensitivity of the cells to IL-2 and diminished suppressive capacity. Results of the study are published in Nature Immunology.

Publications

  1. Konopacki C, Pritykin Y, Rubtsov Y, Leslie CS, Rudensky AY (2019). Transcription factor Foxp1 regulates Foxp3 chromatin binding and coordinates regulatory T cell function. Nat Immunol 20 (2), 232–242

Integrator is a key component of human telomerase RNA biogenesis

Telomeres are special DNA-protein structures that are located at the ends of linear eukaryotic chromosomes. The telomere length determines the proliferation potential of cells. Telomerase is a key component of the telomere length maintenance system. While telomerase is inactive in the majority of somatic cells, its activity determines the clonogenic potential of stem cells as a resource for tissue and organism regeneration. Reactivation of telomerase occurs during the process of immortalization in the majority of cancer cells. Telomerase is a ribonucleoprotein that contains telomerase reverse transcriptase and telomerase RNA components. The RNA processing mechanism of telomerase involves exosome trimming or degradation of the primary precursor. Recent data provide evidence that the competition between the processing and decay of telomerase RNA may regulate the amount of RNA at the physiological level. We show that termination of human telomerase RNA transcription is dependent on its promoter, which engages with the multisubunit complex Integrator to interact with RNA polymerase II and terminate transcription of the human telomerase RNA gene followed by further processing.

Publications

  1. Rubtsova MP, Vasilkova DP, Moshareva MA, Malyavko AN, Meerson MB, Zatsepin TS, Naraykina YV, Beletsky AV, Ravin NV, Dontsova OA (2019). Integrator is a key component of human telomerase RNA biogenesis. Sci Rep 9 (1), 1701
  2. Konopacki C, Pritykin Y, Rubtsov Y, Leslie CS, Rudensky AY (2019). Transcription factor Foxp1 regulates Foxp3 chromatin binding and coordinates regulatory T cell function. Nat Immunol 20 (2), 232–242