Coordination of RNA abundance and transcription rates with cell size has been observed in diverse organisms and isogenic cell populations. However, how cells achieve such ‘size-scaling’ of transcription is unknown. Here we describe a genome-wide siRNA screen to find novel regulators of global RNA production in human cells. We quantify single-cell RNA production rates using metabolic pulse-labelling of RNA and subsequent high-content imaging. Our quantitative, single-cell measurements of DNA, nascent RNA, proliferating cell nuclear antigen...