Walter and Ruth Schubert Family Chair, Professor of Biochemistry, Biophysics and Structural BiologyLab Homepage: https://sites.google.com/site/kcollinslab/
Telomerase RNP structure, biogenesis, function and regulation
The cellular reverse transcriptase telomerase adds simple-sequence repeats to chromosome ends by copying a template within its integral RNA subunit. This new telomeric repeat synthesis balances the loss of repeats that occurs with each round of genome replication. We study telomerase both in vitro, to understand its unique structure and dynamic nucleic acid handling, and in vivo, to understand the complex cellular pathways for active RNP biogenesis and regulation of telomerase action at telomeres. In parallel we are using structural, biochemical, molecular and cellular assays to investigate the assembly and regulation of human telomerase.
Beyond telomerase: biology and biotechnology of retroelements and non-coding RNAs
We have been applying our insights from studies of telomerase to investigations of retroelement reverse transcriptases and non-coding (nc) RNA biogenesis and function. In human cells we have discovered and will expand our studies of new ncRNA processing pathways and ncRNA functions in stress responses and innate immunity. We have begun to apply our understanding of telomerase to illuminate principles for non-LTR retroelement mobility and unique reverse transcriptase properties.
Nguyen THD, Tam J, Wu RA, Greber BJ, Toso D, Nogales E, Collins K. Cryo-EM structure of substrate-bound human telomerase holoenzyme. Nature in press (2018).
Wu RA, Tam J, Collins K. DNA-binding determinants and cellular thresholds for human telomerase repeat addition processivity. EMBO J 36: 1908-27 (2017).
Farley BM, Collins K. Trans-generational function of Tetrahymena Piwi protein Twi8p at distinctive non-coding RNA loci. RNA 23: 530-45 (2017).
Wu RA, Upton HE, Vogan JM, Collins K. Telomerase mechanisms of telomere synthesis. Ann Rev Biochem 86: 439-60 (2017).
Upton HE, Chan H, Feigon J, Collins K. Replication Protein A subunits assemble alternative complexes for general single-stranded DNA binding or telomeric-repeat DNA binding by Tetrahymena telomerase holoenzyme. JBC 292: 217-28 (2017).
Chiba K, Vogan JM, Wu RA, Gill MS, Zhang X, Collins K, Hockemeyer H. Endogenous TERT N-terminal tagging affects human telomerase function at telomeres in vivo. MCB 37 e00541-516 (2017).
Vogan JM, Zhang X, Youmans DT, Regalado SG, Johnson JZ, Hockemeyer D, Collins K. Minimized human telomerase maintains telomeres and resolves endogenous roles of H/ACA proteins, TCAB1, and Cajal bodies. eLife 5: e18221 1-21 (2016).
Wu RA, Dagdas YS, Yilmaz ST, Yildiz , Collins K . Single-molecule imaging of telomerase reverse transcriptase in human telomerase holoenzyme and minimal RNP complexes. eLife 4: e08363 1-26 (2015).
Wan B, Tang T, Upton H, Shuai J, Zhou Y, Li S, Chen J, Brunzelle JS, Zeng Z, Collins K, Wu J, Lei M. The Tetrahymena telomerase p75-p45-p19 subcomplex is a unique CST complex. NSMB 22: 1023-26 (2015).
Jiang J, Chan H, Cash DD, Miracco EJ, Loo RRO, Upton HE, Cascio D, Johnson RO, Collins K, Loo JA, Zhou ZH, Feigon J. Structure of Tetrahymena telomerase reveals previously unknown subunits, functions, and interactions. Science 350: aab4070 1-10 (2015).
Hockemeyer D, Collins K. Control of telomerase action at human telomeres. NSMB 22: 848-52 (2015).
Vogan JM, Collins K. Dynamics of human telomerase holoenzyme assembly and subunit exchange across the cell cycle. JBC 290: 21320-35 (2015).
Upton HE, Hong K, Collins K.Direct single-stranded DNA binding by Teb1 mediates the recruitment of Tetrahymena telomerase to telomeres. MCB 34: 4200-12 (2014).
Wu RA, Collins K. Sequence specificity of human telomerase. PNAS 111: 11234-5 (2014).
Sexton AN, Regalado SG, Lai CS, Cost GJ, O'Neil CM, Urnov FD, Gregory PD, Jaenisch R, Collins K, Hockemeyer D. Genetic and molecular identification of three human TPP1 functions in telomerase action: Recruitment, activation, and homeostasis set-point regulation. Genes Dev 28: 1885-99 (2014).
Katibah GE, Qin Y, Sidote DJ, Yao J, Lambowitz AM, Collins K. Broad and adaptable RNA structure recognition by the human interferon-induced tetratricopeptide repeat protein IFIT5. PNAS 111: 12025-30 (2014).
Upton HE, Hong K, Collins K. Direct single-stranded DNA binding by Teb1 mediates the recruitment of Tetrahymena telomerase to telomeres. MCB 34: 4200-12 (2014).
Wu RA, Collins K. Human telomerase specialization for repeat synthesis by unique handling of primer-template duplex. EMBO J 8: 921-35 (2014)
Collins K, Nilsen TW. Enzyme engineering through evolution: Thermostable recombinant group II intron reverse transcriptases provide new tools for RNA research and biotechnology. RNA 19: 1017-18 (2013).
Hong K, Upton H, Miracco EJ, Jiang J, Zhou ZH, Feigon J, Collins K. Tetrahymena telomerase holoenzyme assembly, activation, and inhibition by domains of the p50 central hub. MCB 33: 3962-71 (2013).
Jiang J, Miracco EJ, Hong K, Eckert B, Chan H, Cash DD, Min B, Zhou ZH*, Collins K, Feigon J. The architecture of Tetrahymena telomerase holoenzyme. Nature 496: 187-192 (2013).
Photo credit: Mark Hanson of Mark Joseph Studios.
Last Updated 2018-04-24