Biogenesis of Telomerase Ribonucleoproteins

Overview

Journal RNA

Specialty Molecular Biology

Date 2012 Aug 10

PMID 22875809

Citations 110

Authors

Emily D Egan

Kathleen Collins

Affiliations

Soon will be listed here.

Abstract

Telomerase adds simple-sequence repeats to the ends of linear chromosomes to counteract the loss of end sequence inherent in conventional DNA replication. Catalytic activity for repeat synthesis results from the cooperation of the telomerase reverse transcriptase protein (TERT) and the template-containing telomerase RNA (TER). TERs vary widely in sequence and structure but share a set of motifs required for TERT binding and catalytic activity. Species-specific TER motifs play essential roles in RNP biogenesis, stability, trafficking, and regulation. Remarkably, the biogenesis pathways that generate mature TER differ across eukaryotes. Furthermore, the cellular processes that direct the assembly of a biologically functional telomerase holoenzyme and its engagement with telomeres are evolutionarily varied and regulated. This review highlights the diversity of strategies for telomerase RNP biogenesis, RNP assembly, and telomere recruitment among ciliates, yeasts, and vertebrates and suggests common themes in these pathways and their regulation.

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References

Cifuentes-Rojas C, Kannan K, Tseng L, Shippen D . Two RNA subunits and POT1a are components of Arabidopsis telomerase. Proc Natl Acad Sci U S A. 2010; 108(1):73-78. PMC: 3017190. DOI: 10.1073/pnas.1013021107. View

Forsythe H, JARVIS J, Turner J, Elmore L, Holt S . Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J Biol Chem. 2001; 276(19):15571-4. DOI: 10.1074/jbc.C100055200. View

Peterson S, Stellwagen A, Diede S, Singer M, Haimberger Z, Johnson C . The function of a stem-loop in telomerase RNA is linked to the DNA repair protein Ku. Nat Genet. 2001; 27(1):64-7. DOI: 10.1038/83778. View

Gallardo F, Olivier C, Dandjinou A, Wellinger R, Chartrand P . TLC1 RNA nucleo-cytoplasmic trafficking links telomerase biogenesis to its recruitment to telomeres. EMBO J. 2008; 27(5):748-57. PMC: 2265757. DOI: 10.1038/emboj.2008.21. View

Gallardo F, Laterreur N, Cusanelli E, Ouenzar F, Querido E, Wellinger R . Live cell imaging of telomerase RNA dynamics reveals cell cycle-dependent clustering of telomerase at elongating telomeres. Mol Cell. 2011; 44(5):819-27. DOI: 10.1016/j.molcel.2011.09.020. View

Girard C, Verheggen C, Neel H, Cammas A, Vagner S, Soret J . Characterization of a short isoform of human Tgs1 hypermethylase associating with small nucleolar ribonucleoprotein core proteins and produced by limited proteolytic processing. J Biol Chem. 2007; 283(4):2060-9. DOI: 10.1074/jbc.M704209200. View

Jady B, Bertrand E, Kiss T . Human telomerase RNA and box H/ACA scaRNAs share a common Cajal body-specific localization signal. J Cell Biol. 2004; 164(5):647-52. PMC: 2172171. DOI: 10.1083/jcb.200310138. View

Seto A, Zaug A, Sobel S, Wolin S, Cech T . Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particle. Nature. 1999; 401(6749):177-80. DOI: 10.1038/43694. View

Egan E, Collins K . An enhanced H/ACA RNP assembly mechanism for human telomerase RNA. Mol Cell Biol. 2012; 32(13):2428-39. PMC: 3434483. DOI: 10.1128/MCB.00286-12. View

10.

Robart A, Collins K . Investigation of human telomerase holoenzyme assembly, activity, and processivity using disease-linked subunit variants. J Biol Chem. 2009; 285(7):4375-86. PMC: 2836042. DOI: 10.1074/jbc.M109.088575. View

11.

Hoareau-Aveilla C, Bonoli M, Caizergues-Ferrer M, Henry Y . hNaf1 is required for accumulation of human box H/ACA snoRNPs, scaRNPs, and telomerase. RNA. 2006; 12(5):832-40. PMC: 1440901. DOI: 10.1261/rna.2344106. View

12.

Theimer C, Jady B, Chim N, Richard P, Breece K, Kiss T . Structural and functional characterization of human telomerase RNA processing and cajal body localization signals. Mol Cell. 2007; 27(6):869-81. DOI: 10.1016/j.molcel.2007.07.017. View

13.

Seto A, Umansky K, Tzfati Y, Zaug A, Blackburn E, Cech T . A template-proximal RNA paired element contributes to Saccharomyces cerevisiae telomerase activity. RNA. 2003; 9(11):1323-32. PMC: 1287054. DOI: 10.1261/rna.5570803. View

14.

Linger B, Morin G, Price C . The Pot1a-associated proteins Tpt1 and Pat1 coordinate telomere protection and length regulation in Tetrahymena. Mol Biol Cell. 2011; 22(21):4161-70. PMC: 3204076. DOI: 10.1091/mbc.E11-06-0551. View

15.

Robart A, Collins K . Human telomerase domain interactions capture DNA for TEN domain-dependent processive elongation. Mol Cell. 2011; 42(3):308-18. PMC: 3097130. DOI: 10.1016/j.molcel.2011.03.012. View

16.

Kiss T, Fayet-Lebaron E, Jady B . Box H/ACA small ribonucleoproteins. Mol Cell. 2010; 37(5):597-606. DOI: 10.1016/j.molcel.2010.01.032. View

17.

Bosoy D, Peng Y, Mian I, Lue N . Conserved N-terminal motifs of telomerase reverse transcriptase required for ribonucleoprotein assembly in vivo. J Biol Chem. 2002; 278(6):3882-90. DOI: 10.1074/jbc.M210645200. View

18.

Lattmann S, Stadler M, Vaughn J, Akman S, Nagamine Y . The DEAH-box RNA helicase RHAU binds an intramolecular RNA G-quadruplex in TERC and associates with telomerase holoenzyme. Nucleic Acids Res. 2011; 39(21):9390-404. PMC: 3241650. DOI: 10.1093/nar/gkr630. View

19.

Teixeira M, Forstemann K, Gasser S, Lingner J . Intracellular trafficking of yeast telomerase components. EMBO Rep. 2002; 3(7):652-9. PMC: 1084187. DOI: 10.1093/embo-reports/kvf133. View

20.

Mitchell J, Cheng J, Collins K . A box H/ACA small nucleolar RNA-like domain at the human telomerase RNA 3' end. Mol Cell Biol. 1998; 19(1):567-76. PMC: 83914. DOI: 10.1128/MCB.19.1.567. View