| Structural highlights
Function
LARP7_TETTS RNA-binding protein required for assembly of the holoenzyme telomerase ribonucleoprotein (RNP) complex (PubMed:15131081, PubMed:15696174, PubMed:16507983, PubMed:17322903, PubMed:20713447, PubMed:22315458, PubMed:22705372). Telomerase is an essential ribonucleoprotein enzyme that copies new telomeric repeats onto chromosome ends by repetitively synthesizing the short telomere-repeat sequence 5'-TTGGGG-3' using an RNA template component TER (PubMed:15696174, PubMed:17322903, PubMed:20713447). TAP65/p65 specifically binds telomerase RNA template TER and is required for biogenesis and placement of the TER stem-terminus element: TAP65/p65 first protects the 3'-end of TER from degradation and acts as a chaperone to correctly fold TER for protein binding; it then bends TER stem-loop IV to position it for interaction of stem-loop IV with catalytic TERT RNA-binding domain (PubMed:15696174, PubMed:17322903, PubMed:20713447, PubMed:22315458, PubMed:22705372).[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
Telomerase is a ribonucleoprotein complex essential for maintenance of telomere DNA at linear chromosome ends. The catalytic core of Tetrahymena telomerase comprises a ternary complex of telomerase RNA (TER), telomerase reverse transcriptase (TERT), and the essential La family protein p65. NMR and crystal structures of p65 C-terminal domain and its complex with stem IV of TER reveal that RNA recognition is achieved by a combination of single- and double-stranded RNA binding, which induces a 105 degrees bend in TER. The domain is a cryptic, atypical RNA recognition motif with a disordered C-terminal extension that forms an alpha helix in the complex necessary for hierarchical assembly of TERT with p65-TER. This work provides the first structural insight into biogenesis and assembly of TER with a telomerase-specific protein. Additionally, our studies define a structurally homologous domain (xRRM) in genuine La and LARP7 proteins and suggest a general mode of RNA binding for biogenesis of their diverse RNA targets.
Structural Basis for Telomerase RNA Recognition and RNP Assembly by the Holoenzyme La Family Protein p65.,Singh M, Wang Z, Koo BK, Patel A, Cascio D, Collins K, Feigon J Mol Cell. 2012 Jun 14. PMID:22705372[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Witkin KL, Collins K. Holoenzyme proteins required for the physiological assembly and activity of telomerase. Genes Dev. 2004 May 15;18(10):1107-18. doi: 10.1101/gad.1201704. Epub 2004 May 6. PMID:15131081 doi:http://dx.doi.org/10.1101/gad.1201704
- ↑ Prathapam R, Witkin KL, O'Connor CM, Collins K. A telomerase holoenzyme protein enhances telomerase RNA assembly with telomerase reverse transcriptase. Nat Struct Mol Biol. 2005 Mar;12(3):252-7. doi: 10.1038/nsmb900. Epub 2005 Feb 6. PMID:15696174 doi:http://dx.doi.org/10.1038/nsmb900
- ↑ O'Connor CM, Collins K. A novel RNA binding domain in tetrahymena telomerase p65 initiates hierarchical assembly of telomerase holoenzyme. Mol Cell Biol. 2006 Mar;26(6):2029-36. doi: 10.1128/MCB.26.6.2029-2036.2006. PMID:16507983 doi:http://dx.doi.org/10.1128/MCB.26.6.2029-2036.2006
- ↑ Stone MD, Mihalusova M, O'connor CM, Prathapam R, Collins K, Zhuang X. Stepwise protein-mediated RNA folding directs assembly of telomerase ribonucleoprotein. Nature. 2007 Mar 22;446(7134):458-61. doi: 10.1038/nature05600. Epub 2007 Feb 25. PMID:17322903 doi:http://dx.doi.org/10.1038/nature05600
- ↑ Berman AJ, Gooding AR, Cech TR. Tetrahymena telomerase protein p65 induces conformational changes throughout telomerase RNA (TER) and rescues telomerase reverse transcriptase and TER assembly mutants. Mol Cell Biol. 2010 Oct;30(20):4965-76. doi: 10.1128/MCB.00827-10. Epub 2010 Aug , 16. PMID:20713447 doi:http://dx.doi.org/10.1128/MCB.00827-10
- ↑ Akiyama BM, Loper J, Najarro K, Stone MD. The C-terminal domain of Tetrahymena thermophila telomerase holoenzyme protein p65 induces multiple structural changes in telomerase RNA. RNA. 2012 Apr;18(4):653-60. doi: 10.1261/rna.031377.111. Epub 2012 Feb 7. PMID:22315458 doi:http://dx.doi.org/10.1261/rna.031377.111
- ↑ Singh M, Wang Z, Koo BK, Patel A, Cascio D, Collins K, Feigon J. Structural Basis for Telomerase RNA Recognition and RNP Assembly by the Holoenzyme La Family Protein p65. Mol Cell. 2012 Jun 14. PMID:22705372 doi:10.1016/j.molcel.2012.05.018
- ↑ Singh M, Wang Z, Koo BK, Patel A, Cascio D, Collins K, Feigon J. Structural Basis for Telomerase RNA Recognition and RNP Assembly by the Holoenzyme La Family Protein p65. Mol Cell. 2012 Jun 14. PMID:22705372 doi:10.1016/j.molcel.2012.05.018
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