A tyrosyl-tRNA synthetase can function similarly to an RNA structure in the Tetrahymena ribozyme

Abstract

GROUP I introns are highly structured RNAs which catalyse their own splicing by guanosine-initiated transesterification reactions^1,2. Their catalytic core is generally stabilized by RNA-RNA interactions within the core and with peripheral RNA structures^3,4. Additionally, some group I introns require proteins for efficient splicing in vivo⁵. The Neurospora CYT-18 protein, the mitochondria! tyrosyl-transfer RNA synthetase (mt TyrRS), promotes splicing of the Neurospora mitochondrial large ribosomal RNA (LSU) and other group I introns by stabilizing the catalytically active structure of the intron core^6–8. We report here that CYT-18 functions similarly to a peripheral RNA structure, PSabc, that stabilizes the catalytic core of the Tetrahymena LSU intron. The CYT-18 protein and PSabc RNA bind to overlapping sites in the intron core, inducing similar conformational changes correlated with splicing activity. Our results show that a protein can play the role of an RNA structure in a catalytic RNA, a substitution postulated for the evolution of nuclear pre-messenger RNA introns from self-splicing introns^9,10.