Heterogeneous nuclear ribonucleoproteins C1 and C2 associate with the RNA component of human telomerase

Here we demonstrate that heterogeneous nuclear ribonucleoproteins (hnRNPs) C1 and C2 can associate directly with the integral RNA component of mammali an telomerase. The binding site for hnRNPs C1 and C2 maps to a 6-base uridy late tract located directly 5' to the template region in the human telomera se RNA (TR) and a 4-base uridylate tract directly 3' to the template in the mouse TR. Telomerase activity is precipitated with antibodies specific to hnRNPs C1 and C2 from cells expressing wild-type human TR but not a variant of the human TR lacking the hnRNPs C1 and C2 binding site, indicating that hnRNPs C1 and C2 require the 6-base uridylate tract within the human TR to associate with the telomerase holoenzyme. In addition, we demonstrate that binding of hnRNPs C1 and C2 to telomerase correlates with the ability of t elomerase to access the telomere. Although correlative, these data do sugge st that the binding of hnRNPs C1 and C2 to telomerase may be important for the ability of telomerase to function on telomeres. The C proteins of the h nRNP particle are also capable of colocalizing with telomere binding protei ns, suggesting that the C proteins may associate with telomeres in vivo. Th erefore, human telomerase is capable of associating Kith core members of th e hnRNP family of RNA binding proteins through a direct and sequence specif ic interaction with the human TR. This is also the first account describing the precise mapping of a sequence in the human TR that is required to asso ciate with an auxiliary component of the human telomerase holoenzyme.