Abstract 2999: Role of heterogeneous nuclear ribonucleoprotein A/Bs in telomere maintenance

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Abstract Heterogeneous nuclear ribonucleoproteins (hnRNPs) constitute a large family of proteins that associate with nascent pre-mRNAs, packaging them into hnRNP particles. In addition to their action as RNA-binding proteins, several members of the hnRNP family are thought to play roles in telomere maintenance because they are known to bind to telomeric DNA and to TERRA RNA, which is now identified as an integral component of telomeric heterochromatin. Using affinity purification and proteomic approach, we have previously shown that the members of hnRNP A/B family are the most abundant proteins in the nuclear extracts that bound specifically to G-strand telomeric DNA. To address if members of hnRNP A/B family are essential components of a functional telomere (i.e., does hnRNP A/Bs play a structural role) and to determine the functional overlap among members of hnRNP A/Bs in telomere length regulation, we initiated to investigate the biological effects of single, double, or triple knock-down of hnRNP A1, A2/B1 or A3. Preliminary results obtained from transient depletion of single hnRNP A1, A2 or A3 by RNA interference (RNAi) indicated that depletion of hnRNP A2 or A3 significantly reduced cell growth and colony formation. The percentage of cells in the sub-G1 phase was increased following the knockdown of hnRNP A2 or A3. In addition, the expression of S-phase kinase-associated protein-2 (skp2) was decreased in the transient knock-down cells. Surprisingly, however, studies of stable clones derived from single knock-down experiments indicated that knock-down of hnRNP A2, but not A1 or A3, produced a profound effect on cellular growth. This effect does not appear to result from reduced viability and/or apoptosis. We noted that an increased expression of hnRNP A1 was always observed in the stable clones depleted of hnRNP A3. Similarly, increased expression of A3 was observed in the cells depleted of hnRNP A1, suggesting that hnRNP A1 and A3 may have functional redundancy in vivo. Works are in progress to determine whether the anti-proliferation effects of depleting hnRNP A/B may result from telomere dysfunction, and to investigate the functional overlap between hnRNP A/Bs using double knock-down approach. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2999. doi:10.1158/1538-7445.AM2011-2999