Sanij et al. reveal how a transcription-promoting protein prevents these genes from getting uptight.
Human cells have rRNA genes aplenty—roughly 200 of them, which are arranged in clusters. Tuning their output is crucial because too little rRNA can stifle cell growth, whereas too much might lead to cancer. A factor that controls rRNA production is the protein UBF. It maintains rRNA genes in a loose conformation that allows transcription, rather than a condensed and inactive state. How UBF achieved this feat was an unanswered question.
To find out more, Sanij et al. used RNAi to trim UBF levels in human cells by 80%. The researchers' analysis ruled out one method that cells often employ to shut down genes permanently—affixing methyl groups. In fact, the team showed, rRNA silencing is reversible, unlike methylation. The researchers think that UBF works by obstructing the H1 linker histone, which helps stabilize nucleosome particles and allows them to condense into higher-order structures. The linker histone's effect is to compact the DNA, thereby silencing genes. But when UBF is present, the histone can't gain access to the DNA.
The study's big surprise came when the researchers measured rRNA output in cells with scant UBF. Instead of plunging, rRNA levels remained constant. The cells compensated by cranking up the activity of the genes that remained turned on. Cells could muster sufficient rRNA even with 90% of the genes shut down. This result indicates that UBF's actions serve another purpose besides adjusting rRNA levels, such as stabilizing DNA.