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Département de Microbiologie et d'Infectiologie, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, Quebec, Canada

Requests for reprints: Benoit Chabot or Raymund Wellinger, Département de Microbiologie et d'Infectiologie, Faculté de Médecine, Université de Sherbrooke, 3001 12th Avenue Nord, Sherbrooke, Quebec, Canada J1H 5N4. Phone: 819-564-5321; Fax: 819-564-5392. E-mail: Benoit.Chabot{at}USherbrooke.ca or Raymund.Wellinger{at}USherbrooke.ca

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.

Received 3/ 1/04; revised 7/26/04; accepted 8/12/04.

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