Abstract: The invention features a modified small nucleolar ribonucleic acid (snoRNA) that directs the conversion of a uridine to a pseudouridine in a target nucleic acid, e.g., RNA, that includes first and second flanking regions located on either side of the uridine. The modified snoRNA includes a ribonucleotide sequence of a box H/ACA snoRNA including a Domain A sequence and a Domain B sequence, or a Domain A sequence and a Domain C sequence, wherein the snoRNA is modified in that the Domain A sequence is replaced by a first recognition sequence complementary to at least three consecutive nucleotides in the first flanking region in the target nucleic acid, and the Domain B or C sequence is replaced by a second recognition sequence complementary to at least three consecutive nucleotides in the second flanking region in the target nucleic acid.

Abstract: The invention features nucleic acid molecules and methods for use in site-specific methylation of ribonucleotides. The methods of the invention can be used to modulate RNA folding, RNA processing, RNA cleavage, and other processes involving sequence-specific recognition of RNA sequences, as well as for promoting RNA stability.

Abstract: New hybrid ribozymes that exhibit the high metabolic stability of small nucleolar ribonucleic acids (snoRNAs), and that cleave target sequences with high efficiencies in either cis (intra-molecular) or trans (inter-molecular) configuration are described. The hybrid ribozymes include (i) a ribozyme catalytic sequence; and (ii) a snoRNA stabilizing motif; wherein the catalytic sequence and the stabilizing motif are arranged to provide the RNA molecule with a three-dimensional configuration in which the catalytic sequence is positioned to interact with a target sequence and the stabilizing motif adopts a conformation that stabilizes the RNA molecule, and additionally enables the RNA molecule to localize in the nucleolus of a cell.