Overview

Telomeres protect chromosome ends from degradation, fusions, and erroneous recombination events; thus, telomere function is essential to maintain genome integrity. Activation of telomere lengthening mechanisms enables cancer cells to attain replicative immortality, which they achieve by expressing the enzyme telomerase or by alternative lengthening of telomeres (ALT). Telomere transcription regulates telomere function and participates in telomere lengthening mechanisms. The telomeric long noncoding RNA TERRA plays pivotal roles in telomere biology and its mechanisms of action are currently being revealed.

Representation of TERRA transcripts

Research directions

We are interested in understanding the functions and mechanisms of action of TERRA in the regulation of telomere lengthening mechanisms and telomere function. We are attracted by the processes controlling TERRA biogenesis, and use extensively imaging approaches, including live imaging and super resolution microscopy, to study the dynamics of TERRA transcripts in fixed and living cells. We work with human cells and are widening our studies using the animal model C. elegans.

Group members

  • Emilio Cusanelli, PI
  • Julieta Rivosecchi, Postdoc
  • Claudio Oss Pegorar, Postdoc
  • Glenda Paola Grupelli, PhD student
  • Marco Pentassuglia, Master student

 

 

 

 

 

 

 

 

 

 

Collaborations

  • Pascal Chartrand, University of Montreal, Canada
  • Verena Jantsch, University of Vienna, Austria
  • Maria Caterina Mione, University of Trento
  • Paolo Macchi, University of Trento
  • Luciano Conti, University of Trento

Selected publications

Bettin N, Grupelli GP, Gialdini I, Goretti E, Cantarelli M, Andolfato M, Soror E, Sontacchi A, Jurikova K, Querido E, Chartrand P, Cusanelli E. TERRA transcripts localize at long telomeres to regulate telomerase access to chromosome ends. Science Advances, 2024, Jun 14;10(24):eadk4387.

Rivosecchi J, Jurikova K, Cusanelli E. Telomere-specific regulation of TERRA and its impact on telomere stability. Seminars in Cell and Developmental Biology, 2024, Apr;157:3-23.

Manzato C, Larini L, Oss Pegorar C, Dello Stritto MR, Jurikova K, Jantsch V, Cusanelli E. TERRA expression is regulated by the telomere-binding proteins POT-1 and POT-2 in Caenorhabditis elegans. Nucleic Acids Research, 2023, 51(19):10681-10699.

Rivosecchi J, Cusanelli E. TERRA beyond cancer: the biology of telomeric repeat-containing RNAs in somatic and germ cells. Frontiers in Aging, 2023, 4:1224225.

Savoca V, Rivosecchi J, Gaiatto A, Rossi A, Mosca R, Gialdini I, Zubovic L, Tebaldi T, Macchi P, Cusanelli E. TERRA stability is regulated by RALY and polyadenylation in a telomere-specific manner. Cell Reports, 42, 2023, 42(4):112406.

 Jurikova K, De Wulf P, Cusanelli E. Nuclear periphery and telomere maintenance: TERRA joins the stage. Trends in Genetics, 2021, 37(7):608-611.

Idilli AI, Pagani F, Kerschbamer E, Berardinelli F, Bernabé M, Cayuela ML, Piazza S, Poliani PL, Cusanelli E, Mione MC. Changes in the expression of pre-replicative complex genes in hTERT and ALT pediatric brain tumors. Cancers, 2020, 12(4). 

Idilli AI, Cusanelli E, Pagani F, Berardinelli F, Bernabé M, Cayuela ML, Poliani PL, Mione MC. Expression of TERT prevents ALT in zebrafish brain tumors. Frontiers in Cell and Developmental Biology, 2020, 8(65).

Bettin N, Oss Pegorar C, Cusanelli E. The emerging roles of TERRA in telomere maintenance and genome stability. Cells, 2019, 8(3), 246.

Avogaro L, Oss Pegorar C, Bettin N, Cusanelli E. Generation of cancer cell clones to visualize telomeric repeat-containing RNA TERRA expressed from a single telomere in living cells. Journal of Visualized Experiments, 2019, (143): e58790.

Avogaro L, Querido E, Dalachi M, Jantsch M, Chartrand P, Cusanelli E. Live-cell imaging reveals the dynamics and function of single-telomere TERRA molecules in cancer cells. RNA Biology, 2018, 15(6):787-796.

Perez-Romero CA, Lalonde M, Chartrand P, Cusanelli E. Induction and relocalization of telomeric repeat-containing RNAs during diauxic shift in budding yeast. Current Genetics, 2018, 64(5):1117-1127.

Moradi-Fard S, Sarthi J, Tittel-Elmer M, Lalonde M, Cusanelli E, Chartrand P, Cobb J. Smc5/6 is a telomere-associated complex that regulates Sir4 binding and TPE. PLOS Genetics, 2016, 12(8): e1006268.

Cusanelli E* and Chartrand P. Telomeric repeat-containing RNA TERRA: a noncoding RNA connecting telomere biology to genome integrity. Frontiers in Genetics, 2015, 6: 143. * Corresponding author.

Cusanelli E and Chartrand P. Telomeric non-coding RNA TERRA in telomere biology. Wiley Interd. Rev. RNA, 2014, 5(3): 407-419.

Cusanelli E, Perez Romero CA, Chartrand P. Telomeric non-coding RNA TERRA is induced by telomere shortening to nucleate telomerase molecules at short telomeres. Molecular Cell, 2013, 51(6): 780-791. Highlighted by Faculty of 1000

Funding

  • 2024, MUR PNRR, CN for gene therapy and drugs based on RNA technologies
  • 2020, My First AIRC Grant
  • 2016, MUR, Rita Levi Montalcini program