The RNA Pol Ⅱ sub-complex hsRpb4/7 is required for viability of multiple human cell lines

The evolutionarily conserved RNA Polymerase Ⅱ Rpb4/7 sub-complex has been thoroughly studied in yeast and impacts gene expression at multiple levels including transcription,mRNA processing and decay.In addition Rpb4/7 exerts differential effects on gene expression in yeast and Rpb4 is not obligatory for yeast(S.cerevisiae)survival.Specialised roles for human(hs)Rpb4/7 have not been extensively described and we have probed this question by depleting hsRpb4/7 in established human cell lines using RNA interference.We find that Rpb4/7 protein levels are inter-dependent and accordingly,the functional effects of depleting either protein are co-incident.hsRpb4/7 exhibits gene-specific effects and cells initially remain viable upon hsRpb4/7 depletion.However prolonged hsRpb4/7 depletion is cytotoxic in the range of cell lines tested.Protracted cell death occurs by an unknown mechanism and in some cases is accompanied by a pronounced elongated cell morphology.In conclusion we provide evidence for a gene-specific role of hsRpb4/7 in human cell viability.