RNA as a flexible scaffold for proteins: yeast telomerase and beyond.

Yeast telomerase, the enzyme that adds a repeated DNA sequence to the ends of the chromosomes, consists of a 1157- nucleotide RNA (TLC1) plus several protein subunits: the telomerase reverse transcriptase Est2p, the regulatory subunit Est1p, the nonhomologous end-joining heterodimer Ku, and the seven Sm proteins involved in ribonucleoprotein (RNP) maturation. The RNA subunit provides the template for telomeric DNA synthesis. In addition, we have reported evidence that it serves as a flexible scaffold to tether the proteins into the complex. More generally, we consider the possibility that RNPs may be considered in three structural categories: (1) those that have specific structures determined in large part by the RNA, including RNase P, other ribozyme-protein complexes, and the ribosome; (2) those that have specific structures determined in large part by proteins, including many small nuclear RNPs (snRNPs) and small nucleolar RNPs (snoRNPs); and (3) flexible scaffolds, with no specific structure of the RNP as a whole, as exemplified by yeast telomerase. Other candidates for flexible scaffold structures are other telomerases, viral IRES (internal ribosome entry site) elements, tmRNA (transfer-messenger RNA), the SRP (signal recognition particle), and Xist and roX1 RNAs that alter chromatin structure to achieve dosage compensation.