The emerging role of triple helices in RNA biology

The ability of RNA to form sophisticated secondary and tertiary structures enables it to perform a wide variety of cellular functions. One tertiary structure, the RNA triple helix, was first observed in vitro over 50 years ago, but biological activities for triple helices are only beginning to be appreciated. The recent determination of several RNA structures has implicated triple helices in distinct biological functions. For example, the SAM-II riboswitch forms a triple helix that creates a highly specific binding pocket for S-adenosylmethionine. In addition, a triple helix in the conserved pseudoknot domain of the telomerase-associated RNA TER is essential for telomerase activity. A viral RNA cis-acting RNA element called the ENE contributes to the nuclear stability of a viral noncoding RNA by forming a triple helix with the poly(A) tail. Finally, a cellular noncoding RNA, MALAT1, includes a triple helix at its 3'-end that contributes to RNA stability, but surprisingly also supports translation. These examples highlight the diverse roles that RNA triple helices play in biology. Moreover, the dissection of triple helix mechanisms has the potential to uncover fundamental pathways in cell biology.