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The architecture of Tetrahymena telomerase (926.2)
Author(s) -
Feigon Juli
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.926.2
Subject(s) - telomerase , tetrahymena , telomere , protein subunit , chemistry , processivity , microbiology and biotechnology , telomerase reverse transcriptase , biology , dna , dna replication , biochemistry , gene
Telomerase is an RNA‐protein complex that extends the ends of linear chromosomes, and is a highly regulated determinant of cellular aging, stem cell renewal, and tumorigenesis. We have obtained the 3D structure of endogenously assembled Tetrahymena thermophila telomerase holoenzyme at 25 Å resolution using electron microscopy (EM). The 7 protein subunits and the stem‐loop 2 region of TER have been localized in the 3D structure by affinity labeling. Fitting with the available high‐resolution structures, including a p65‐TER complex, reveals the organization of TERT, TER, and p65 in the RNP catalytic core. Among the other holoenzyme proteins, p50 has an unanticipated role as a hub between the RNP catalytic core, p75‐p19‐p45 subcomplex, and the DNA‐binding Teb1. A complete in vitro holoenzyme reconstitution correlates activity with structure. This first physical and functional network architecture of a telomerase holoenzyme provides unprecedented detail about the structure of the RNP catalytic core and reveals the organization of holoenzyme subunits that confer processivity and bridge telomerase to telomeres. J. Jiang, E.J. Miracco, K. Hong, B. Eckert, H. Chan, D.D. Cash, B. Min, Z. H. Zhou , K. Collins , and J. Feigon , “The architecture of Tetrahymena telomerase holoenzyme”, Nature , 496 , 187‐182 (2013). K. Hong, H. Upton, E.J. Miracco, J. Jiang, Z.H. Zhou, J. Feigon , and K. Collins , “Tetrahymena telomerase holoenzyme assembly, activation, and inhibition by domains of the p50 central hub”, Mol Cell Biol . 33 , 3962‐3971 (2013). M. Singh, Z. Wang, B.‐K. Koo, A. Patel, D. Cascio, K. Collins, and J. Feigon : “Structural basis for telomerase RNA recognition and RNP assembly by the holoenzyme La family protein p65”, Mol Cell 47 , 16‐26 (2012). Grant Funding Source : NSF MCB1022379, NIH GM48123