Telomerase-binding protein EST1A

Definition:

Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. May have a general role in telomere regulation. Promotes in vitro the ability of TERT to elongate telomeres. Overexpression induces telomere uncapping, chromosomal end-to-end fusions (telomeric DNA persists at the fusion points) and did not perturb TRF2 telomeric localization. Binds to the single-stranded 5'-(GTGTGG)(4)GTGT-3' telomeric DNA, but not to a telomerase RNA template component (TER).; Plays a role in nonsense-mediated mRNA decay. Is thought to provide a link to the mRNA degradation machinery as it has endonuclease activity required to initiate NMD, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation. Degrades single-stranded RNA (ssRNA), but not ssDNA or dsRNA.

References:

[1]. Bryan E Snow, et al. Functional conservation of the telomerase protein Est1p in humans. Curr Biol. 2003 Apr 15;13(8):698-704. [Content Brief]

[2]. Andrea B Eberle, et al. SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells. Nat Struct Mol Biol. 2009 Jan;16(1):49-55. [Content Brief]

[3]. Eric Huntzinger, et al. SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan. RNA. 2008 Dec;14(12):2609-17. [Content Brief]

[4]. Filip Glavan, et al. Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex. EMBO J. 2006 Nov 1;25(21):5117-25. [Content Brief]

[5]. Andrew S Venteicher, et al. A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis. Science. 2009 Jan 30;323(5914):644-8. [Content Brief]

[6]. Patrick Reichenbach, et al. A human homolog of yeast Est1 associates with telomerase and uncaps chromosome ends when overexpressed. Curr Biol. 2003 Apr 1;13(7):568-74. [Content Brief]

[7]. Isao Kashima, et al. SMG6 interacts with the exon junction complex via two conserved EJC-binding motifs (EBMs) required for nonsense-mediated mRNA decay. Genes Dev. 2010 Nov 1;24(21):2440-50. [Content Brief]

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