Structure and function of the T-loop structural motif in noncoding RNAs

The T-loop is a frequently occurring five-nucleotide motif found in the structure of noncoding RNAs where it is commonly assumed to play an important role in stabilizing the tertiary RNA structure by facilitating long-range interactions between different regions of the molecule. T-loops were first identified in tRNA(Phe) and a formal consensus sequence for this motif was formulated and later revised based on analyses of the crystal structures of prokaryotic ribosomal RNAs and RNase P and the corresponding primary sequence of their orthologues. In the past decade, several new structures of large RNA molecules have been added to the RCSB Protein Data Bank, including the eukaryotic ribosome, a self-splicing group II intron, numerous synthetases in complex with their cognate transfer RNAs (tRNAs), transfer-messenger RNA (tmRNA) in complex with SmpB, several riboswitches, and a complex of bacterial RNase P bound to its tRNA substrate. In this review, the search for T-loops is extended to these new RNA molecules based on the previously established structure-based criteria. The review highlights and discusses the function and additional roles of T-loops in four broad categories of RNA molecules, namely tRNAs, ribosomal RNAs (rRNAs), P RNAs, and RNA genetic elements. Additionally, the potential application for T-loops as interaction modules is also discussed.