Differential requirements for H/ACA ribonucleoprotein components in cell proliferation and response to DNA damage

摘要: H/ACA ribonucleoproteins (RNPs) are comprised of four conserved proteins, dyskerin, NHP2, NOP10, and GAR1, a function-specifying, noncoding RNA. RNPs contribute to telomerase assembly stabilization, posttranscriptional processing nascent ribosomal RNA spliceosomal However, very little is known about the coordinated action proteins in other biologic processes. As described herein, we observed differential requirement for cell proliferation identified possible reliance these factors regulation specific DNA damage biomarkers. In particular, GAR1 expression was upregulated following exposure all forms genotoxic stress tested. contrast, levels were either reduced or unaffected. Only showed an altered subcellular localization with shift from nucleolus nucleoplasm after ultraviolet-C irradiation doxorubicin treatments. Transient siRNA-mediated depletion dyskerin arrested proliferation, whereas loss NHP2 NOP10 had no effect. Finally, respectively, limited accumulation individual responses dependent upon type incurred. general, most suppressive effect on biomarkers Since stress, contribution each protein activation not equivalent, this suggests possibility that at least some notably may potentially function independently their respective roles within RNP complexes.