TERRA stability is regulated by RALY and polyadenylation in a telomere-specific manner
Valeria Savoca,
Julieta Rivosecchi,
Alice Gaiatto,
Annalisa Rossi,
Riccardo Mosca,
Irene Gialdini,
Lorena Zubovic,
Toma Tebaldi,
Paolo Macchi,
Emilio Cusanelli
Affiliations
Valeria Savoca
Laboratory of Cell Biology and Molecular Genetics, Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, via Sommarive 9, 38123 Trento, Povo, Italy
Julieta Rivosecchi
Laboratory of Cell Biology and Molecular Genetics, Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, via Sommarive 9, 38123 Trento, Povo, Italy
Alice Gaiatto
Laboratory of Cell Biology and Molecular Genetics, Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, via Sommarive 9, 38123 Trento, Povo, Italy
Annalisa Rossi
Laboratory of Molecular and Cellular Neurobiology, Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, via Sommarive 9, 38123 Trento, Povo, Italy
Riccardo Mosca
Laboratory of Cell Biology and Molecular Genetics, Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, via Sommarive 9, 38123 Trento, Povo, Italy
Irene Gialdini
Laboratory of Cell Biology and Molecular Genetics, Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, via Sommarive 9, 38123 Trento, Povo, Italy
Lorena Zubovic
Laboratory of Molecular and Cellular Neurobiology, Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, via Sommarive 9, 38123 Trento, Povo, Italy
Toma Tebaldi
Laboratory of RNA and Disease Data Science, Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, via Sommarive 9, 38123 Trento, Povo, Italy; Section of Hematology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT, USA
Paolo Macchi
Laboratory of Molecular and Cellular Neurobiology, Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, via Sommarive 9, 38123 Trento, Povo, Italy; Corresponding author
Emilio Cusanelli
Laboratory of Cell Biology and Molecular Genetics, Department of Cellular, Computational and Integrative Biology - CIBIO, University of Trento, via Sommarive 9, 38123 Trento, Povo, Italy; Corresponding author
Summary: Telomeric repeat-containing RNA (TERRA) is a long non-coding RNA transcribed from telomeres that plays key roles in telomere maintenance. A fraction of TERRA is polyadenylated, and the presence of the poly(A) tail influences TERRA localization and stability. However, the mechanisms of TERRA biogenesis remain mostly elusive. Here, we show that the stability of TERRA transcripts is regulated by the RNA-binding protein associated with lethal yellow mutation (RALY). RALY depletion results in lower TERRA levels, impaired localization of TERRA at telomeres, and ultimately telomere damage. Importantly, we show that TERRA polyadenylation is telomere specific and that RALY preferentially stabilizes non-polyadenylated TERRA transcripts. Finally, we report that TERRA interacts with the poly(A)-binding protein nuclear 1 (PABPN1). Altogether, our results indicate that TERRA stability is regulated by the interplay between RALY and PABPN1, defined by the TERRA polyadenylation state. Our findings also suggest that different telomeres may trigger distinct TERRA-mediated responses.
