Targeting heterogeneous nuclear ribonucleoparticule A1 and A2 proteins by RNA interference promotes cell death in transformed but not in normal mouse cell lines.
The heterogeneous nuclear ribonucleoparticule A1 and A2 proteins can bind to vertebrate single-stranded telomeric sequences. Moreover, changes in the levels of heterogeneous nuclear ribonucleoparticule A1 can influence telomere length in mouse and human cells. We have shown previously that the combined knockdown of A1 and A2 proteins in human transformed cells promotes apoptosis. In contrast, a similar reduction in A1 and A2 expression in normal mortal human cell lines does not induce cell death. Here, we show that a variety of mouse cell lines display a similar behavior on reduction of A1 and A2 protein levels using small interfering RNA. In addition, the expression of the mouse A1 cDNA protects human HeLa cells from apoptosis when human A1 and A2 proteins are targeted by RNA interference. Lastly, we show that knockdown of A1 and A2 expression also impairs the growth of a human transformed cell line that does not express telomerase. These results firmly establish A1 and A2 as proteins required for the viability of transformed murine and human cells, irrespective of the status of telomerase expression or the length of the double-stranded telomeric repeat.
Département de Microbiologie et d'Infectiologie, Faculté de Médecine, Université de Sherbrooke, 3001 12th Avenue Nord, Sherbrooke, Quebec J1H 5N4, Canada.
Caroline
C
Patry
Bruno
B
Lemieux
Raymund J
RJ
Wellinger
Benoit
B
Chabot
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016923:Cell Death; D002460:Cell Line; D002461:Cell Line, Transformed; D002470:Cell Survival; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006367:HeLa Cells; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000648:ultrastructure; D013997:Time Factors; D014162:Transfection
D018076:DNA, Complementary; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034741:RNA, Small Interfering; C439768:hnRNP A2; D019098:Telomerase