Work

Structure and sequence elements of the CR4/5 domain of medaka telomerase RNA important for telomerase function

Year: 2013

Type: article

Abstract: Telomerase is a unique reverse transcriptase that maintains the 3' ends of eukaryotic chromosomes by adding tandem telomeric repeats. The RNA subunit (TR) of vertebrate telomerase provides a template for reverse transcription, contained within the conserved template/pseudoknot domain, and a conserved regions 4 and 5 (CR4/5) domain, all essential for catalytic activity. We report the nuclear magnetic resonance (NMR) solution structure of the full-length CR4/5 domain from the teleost fish medaka (Oryzias latipes). Three helices emanate from a structured internal loop, forming a Y-shaped structure, where helix P6 stacks on P5 and helix P6.1 points away from P6. The relative orientations of the three helices are Mg2+ dependent and dynamic. Although the three-way junction is structured and has unexpected base pairs, telomerase activity assays with nucleotide substitutions and deletions in CR4/5 indicate that none of these are essential for activity. The results suggest that the junction is likely to change conformation in complex with telomerase reverse transcriptase and that it provides a flexible scaffold that allows P6 and P6.1 to correctly fold and interact with telomerase reverse transcriptase.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkt1276

Authors: Nak-Kyoon Kim, Qi Zhang, Juli Feigon

Institutions: University of North Carolina at Chapel Hill, University of California, Los Angeles, Korea Institute of Science and Technology

Language: English

Topic: Telomeres, Telomerase, and Senescence

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

Open Access status: gold

Estimated APC paid: $3,992

Funders: Korea Institute of Science and Technology, National Institutes of Health, National Institute of General Medical Sciences