Abstract
BACKGROUND:Pseudouridine (Ψ) is the most abundant post-transcriptionally modified nucleotide found in RNA.Ψ is clustered in functionally important and evolutionary conserved regions of RNAs in all three domains of life.Pseudouridylation is catalyzed by two distinct mechanisms:an RNA-independent and an RNA-dependent mechanism.The former involves a group of stand-alone protein enzymes,and the latter involves a family of complex enzymes called box H/ACA RNPs,each of which consists of one RNA (box H/ACA RNA) and a set of four core proteins.Over the years,the mechanism of RNA-dependent pseudouridylation has been extensively studied.The crystal structures of partial and complete box H/ACA RNP have been solved.However,the detailed picture of RNA-dependent pseudouridylation is still not entirely clear.OBJECTIVE:In this work,we review what is known about box H/ACA RNP and the mechanism by which box H/ACA RNP catalyzes RNA-dependent pseudouridylation.We also discuss some examples of the dual nature and redundancy of box H/ ACA RNPs that deviate from the usual mechanism.METHODS:A methodical literature search was performed using the Pubmed central search engine and Intemational Digital Publishing Forum (EPUB) using the following keywords:"pseudouridylation," "pseudouridine," and "box H/ACA RNP." The necessary information was extracted and cited.RESULTS:A detailed introduction is made including the discovery,mechanism and crystal structure of box H/ACA RNP.Three sequence/structural requirements for box H/ACA RNA-guided pseudouridylation are discussed and the exceptions to those rules are explored.CONCLUSION:Over the years,box H/ACA RNP-catalyzed pseudouridylation has been extensively studied,generating fruitful results.However,a detailed picture regarding the mechanism of this reaction is still to be deciphered.More work is needed to fully understand box H/ACA RNP-catalyzed pseudouridylation.
基金项目
work carried out in the Yu laboratory was supported from NIH (to Y-T Yu)(GM104077)
NETL
NSTL
维普
万方数据