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

Nucleic Acids Research
Nak-Kyoon KimJuli Feigon

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.

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Citations

Oct 21, 2015·Nucleic Acids Research·Georgeta ZemoraChristina Waldsich
Jul 1, 2016·RNA Biology·Joshua D Podlevsky, Julian J-L Chen
Aug 18, 2016·Proceedings of the National Academy of Sciences of the United States of America·Yaqiang WangJuli Feigon
Sep 21, 2016·Genes·Deanna Elise MacNeilChantal Autexier
Dec 10, 2016·Biochemistry·William J Martin, Nicholas J Reiter
Dec 3, 2016·Nucleic Acids Research·Darian D Cash, Juli Feigon
Dec 25, 2015·PLoS Genetics·Albino BacollaKaren M Vasquez
Mar 17, 2017·Annual Review of Biophysics·Henry ChanJuli Feigon
Apr 27, 2019·Wiley Interdisciplinary Reviews. RNA·Huaqun Zhang, Sarah C Keane
Nov 16, 2019·Cellular and Molecular Life Sciences : CMLS·Eric M SmithJayakrishnan Nandakumar
Nov 11, 2017·Wiley Interdisciplinary Reviews. RNA·Cherie MusgroveMichael D Stone
Aug 28, 2019·Cold Spring Harbor Perspectives in Biology·Yaqiang WangJuli Feigon
May 3, 2018·Nucleic Acids Research·Nina M FischerDavid van der Spoel
May 6, 2014·Nature Structural & Molecular Biology·Jing HuangMing Lei
Nov 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yaqiang WangJuli Feigon
Apr 6, 2021·The Journal of Physical Chemistry. B·Jingru Xie, Aaron T Frank

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Methods Mentioned

BETA
NMR
nuclear magnetic resonance
cross-linking
electrophoresis
Electrophoretic mobility shift assay
cross-linking studies

Software Mentioned

TERT
Mfold
PyMOL
MOLMOL
SWISS MODEL workplace
Sparky
XPLOR
TOPSPIN
XWINNMR
RAMAH

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