New publication from the Molecular Biology and Biochemistry Laboratory focusing on novel mechanisms of regulation of ribosomal RNA (rRNA) transcription in mammalian cells

Ph.D. student Andria Theophanous from the Molecular Biology and Biochemistry Laboratory (mbblab.net) was lead author of a new publication in the Journal of Biological Chemistry focusing on novel mechanisms of regulation of ribosomal RNA (rRNA) transcription in mammalian cells. The team of authors found that depletion of transcription factor UBF leads to a drastic and large-scale re-adaptation profoundly affecting expression of major factors involved in different aspects of rRNA transcription, namely preinitiation complex proteins TAF1A-C, TBP and RRN3, termination factor TTF1, chromatin modifier CCTF, cyclin D, important Ser484 phosphorylation that renders UBF transcription-competent, and also master transcription factor C-MYC. Growth-related mTOR signaling was also downregulated with the fractions of active phospho-S6 Kinase and pEIF4E translation initiation factor reduced, similar to phosphorylated cell cycle regulator retinoblastoma, pRB, positive regulator of UBF availability/rRNA transcription. The study additionally identified a novel mode of transcriptional regulation via the modulation of gene expression of RNA polymerase I itself; this mechanism was nutrient concentration-responsive and extended not only to UBF-depleted but also occurred in wild-type cells, suggesting that regulation of rRNA transcription may not be restricted to modulation of POL1 promoter binding/elongation rate or the modulation of the number of active rDNA genes, as it is traditionally defined.

Andria defended her thesis successfully in December 2023 and has completed her doctoral studies.

Publication
Theophanous A, Christodoulou A, Mattheou C, Sibai DS, Moss T, Santama N. Transcription factor UBF depletion in mouse cells results in downregulation of both downstream and upstream elements of the rRNA transcription network. J Biol Chem. 2023 Oct;299(10):105203. doi: 10.1016/j.jbc.2023.105203. Epub 2023 Sep 1. PMID: 37660911; PMCID: PMC10558777.

The full article is available here: www.jbc.org/article/S0021-9258(23)02231-7/fulltext

A popularised summary of the scientific article is hosted on the Atlas of Science (https://atlasofscience.org/making-christmas-trees-under-duress-or-how-cells-regulate-the-production-of-ribosomal-rna/), a platform that highlights selected new articles from the scientific literature with the aim of dissemination to the international media and the general public.