Walter and Ruth Schubert Family Chair, Professor of Biochemistry, Biophysics and Structural Biology

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Research Interests

We are applying our insights from decades of studying telomerase and telomere maintenance to investigate eukaryotic retroelements, their reverse transcriptases, and the biogenesis and RNP assembly of processed RNA used as template for nick-primed cDNA synthesis. Site-specific targeting of transgene cDNA insertion has promise as a genome engineering method complementary to CRISPR/Cas. Also, retroelement reverse transcriptases have fascinating biochemical properties that we are discovering and exploiting for RNA-seq. Our new approaches for cDNA library production capture comprehensive, end-to-end RNA sequence inventory of even fragmented or damaged RNAs.

Selected Publications

Boyle JM, Hennick KM, Regalado SG, Vogan JM, Zhang X, Collins K, Hockemeyer D. Telomere length set point regulation in human pluripotent stem cells critically depends on the shelterin protein TPP1. Mol Biol Cell doi: 10.1091/mbc.E19-08-0447 (2020).

Nguyen THD, Collins K, Nogales E. Telomerase structures and regulation: shedding light on the chromosome end. Curr Opin Struct Biol 55: 185-193 (2019).

Deshpande AP, Collins K. Mechanisms of template handling and pseudoknot folding in human telomerase and their manipulation to expand the sequence repertoire of processive repeat synthesis. Nucleic Acids Res 2018 46:7886-7901 (2018).

Nguyen THD, Tam J, Wu RA, Greber BJ, Toso D, Nogales E, Collins K. Cryo-EM structure of substrate-bound human telomerase holoenzyme. Nature 557: 190-5 (2018).

Wu RA, Upton HE, Vogan JM, Collins K. Telomerase mechanisms of telomere synthesis. Ann Rev Biochem 86: 439-60 (2017).

Wu RA, Tam J, Collins K. DNA-binding determinants and cellular thresholds for human telomerase repeat addition processivity. EMBO J 36: 1908-27 (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: e00541-16 (2017).

Farley BM, Collins K. Trans-generational function of Tetrahymena Piwi protein Twi8p at distinctive non-coding RNA loci. RNA 23: 530-45 (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).

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 (2016).

Wu RA, Dagdas YS, Yilmaz ST, Yildiz A, Collins K. Single-molecule imaging of telomerase reverse transcriptase in human telomerase holoenzyme and minimal RNP complexes. eLife 4: e08363 1-26 (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).

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: 1023-6 (2015).

Hockemeyer D, Collins K. Control of telomerase action at human telomeres. NSMB 2015 Nov;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).

Wu RA, Collins K. Sequence specificity of human telomerase. PNAS 111: 11234-5 (2014). PDF

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). PDF

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). PDF

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). PDF

Wu RA, Collins K. Human telomerase specialization for repeat synthesis by unique handling of primer-template duplex. EMBO J. 33: 921-35 (2014). PDF

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). PDF

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: 187-92 (2013). PDF

Katibah GE, Lee HJ, Huizar JP, Vogan JM, Alber T, Collins K. tRNA binding, structure, and localization of the human interferon-induced protein IFIT5. Mol Cell49: 743-50 (2013). PDF

Collins K, Nilsen TW. Enzyme engineering through evolution: Thermostable recombinant group II intron reverse transcriptases provide new tools for RNA research and biotechnology. RNA 1017-8 (2013). PDF

Egan ED, Collins K. Biogenesis of telomerase ribonucleoproteins. RNA 18: 1747-59 (2012). PDF

Couvillion MT, Bounova G, Purdom E, Speed TP, Collins K. A Tetrahymena Piwi bound to mature tRNA 3' fragments activates the exonuclease Xrn2 for RNA processing in the nucleus. Mol Cell 48: 509-20 (2012). PDF

Sexton AN, Youmans DT, Collins K. Specificity requirements for human telomere protein interaction with telomerase holoenzyme. JBC 287: 4455-64 (2012). PDF

Talsky KB, Collins K. Strand-asymmetric endogenous Tetrahymena small RNA production requires a previously uncharacterized uridylyltransferase protein partner. RNA 18: 1553-62 (2012). PDF

Singh M, Wang Z, Koo B, 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 47: 16-26 (2012). PDF

Egan ED, Collins K. An enhanced H/ACA RNP assembly mechanism for human telomerase RNA. MCB 32: 2428-39 (2012). PDF

Eckert B, Collins K. Roles of the telomerase reverse transcriptase N-terminal domain in the assembly and activity of Tetrahymena telomerase holoenzyme.JBC 287: 12805-14 (2012). PDF

Andersen KL, Collins K. Several RNase T2 enzymes function in induced tRNA and rRNA turnover in the ciliate Tetrahymena. Mol Biol Cell 23: 36-44 (2012). PDF

Fass JN, Joshi NA, Couvillion MT, Bowen J, Gorovsky MA, Hamilton EP, Orias O, Hong K, Coyne RS, Eisen JA, Chalker DL, Lin D, Collins K. Genome-scale analysis of programmed DNA elimination sites in Tetrahymena thermophila. G3: Genes, Genomes, Genetics 1: 515-22 (2011). PDF

Collins K. Single-stranded DNA repeat synthesis by telomerase. Current Opinion in Chemical Biology 15: 643-8 (2011). PDF

Zeng Z, Min B, Huang J, Hong K, Yang Y, Collins K, Lei M. Structural basis for Tetrahymena telomerase processivity factor Teb1 binding to single-stranded telomeric-repeat DNA. PNAS 108: 20357-61 (2011). PDF

Robart AR, Collins K. Human telomerase domain interactions capture DNA for TEN-domain-dependent processive elongation. Mol Cell 42: 308-18 (2011). PDF

Sexton AN, Collins K. The 5' guanosine tracts of human telomerase RNA are recognized by the G-quadruplex binding domain of the RNA helicase DHX36 and function to increase RNA accumulation. MCB 31: 736-43 (2011). PDF

Robart AR, Collins K. Investigation of human telomerase holoenzyme assembly, activity, and processivity using disease-linked subunit variants. JBC 285: 4375-86 (2010). PDF

Robart AR, O'Connor CM, Collins K. Ciliate telomerase RNA loop IV nucleotides promote hierarchical RNP assembly and holoenzyme stability. RNA 16: 563-71 (2010). PDF

Madinger CL, Collins K, Fields LG, Taron CH, Benner JS. Constitutive secretion in Tetrahymena thermophila. Euk Cell 9: 674-81 (2010). PDF

Egan ED, Collins K. Specificity and stoichiometry of subunit interactions in the human telomerase holoenzyme assembled in vivo. MCB 30: 2775-86 (2010). PDF

Min B, Collins K. Multiple mechanisms for elongation processivity within the reconstituted Tetrahymena telomerase holoenzyme. JBC 285: 16434-43 (2010). PDF

Kim N, Theimer CA, Mitchell JR, Collins K, Feigon J. Effect of pseudouridylation on the structure and activity of the catalytically essential P6.1 hairpin in human telomerase RNA. NAR 38: 6746-56 (2010). PDF

Talsky KB, Collins K. Initiation by a eukaryotic RNA-dependent RNA polymerase requires looping of the template end and is influenced by the template-tailing activity of an associated uridyltransferase. JBC 285: 27614-23 (2010). PDF

Couvillion MT, Sachidanandam R, Collins K. A growth-essential Tetrahymena Piwi protein carries tRNA fragment cargo. Genes Dev 24: 2742-7 (2010). PDF

Lee SR, Talsky KB, Collins K. A single RNA-dependent RNA polymerase assembles with mutually exclusive nucleotidyl transferase subunits to direct different pathways of small RNA biogenesis. RNA 15: 1362-74 (2009). PDF

Couvillion MT, Lee SR, Hogstad B, Malone CD, Tonkin LA, Sachidanandam R, Hannon GJ, Collins K. Sequence, biogenesis, and function of diverse small RNA classes bound to the Piwi-family proteins of Tetrahymena thermophila. Genes Dev 23: 2016-32 (2009). PDF

Min B, Collins K. An RPA-related sequence-specific DNA binding subunit of telomerase holoenzyme is required for elongation processivity and telomere maintenance. Mol Cell 36: 609-19 (2009). PDF

Hogg JR, Collins K. Structured non-coding RNAs and the RNP renaissance. Current Opinion in Chemical Biology 12: 684-9 (2008). PDF

Collins K. Physiological assembly and activity of human telomerase complexes. Mechanisms of Ageing and Development 129: 91-8 (2008). PDF

Book and Book Chapters

Collins K, Ed. Tetrahymena thermophila. Methods in Cell Biology Volume 109. Academic Press (2012). ISBN: 9780123859679

Collins K. "Perspectives on the ciliated protozoan Tetrahymena thermophila" in Methods in Cell Biology 109: 1-7 (2012).

Couvillion MT, Collins K. "Biochemical approaches including the design and use of strains expressing epitope-tagged proteins" in Methods in Cell Biology 109: 347-355 (2012).

Blackburn EH, Collins K. "Telomerase: an RNP enzyme synthesizes DNA" in RNA Worlds, JF Atkins, TR Cech and RF Gesteland, Eds. Cold Spring Harbor Laboratory Press (2010). PDF

Photo credit: Mark Hanson of Mark Joseph Studios.

Last Updated 2018-04-24