Regulation of telomere metabolism by the RNA processing protein Xrn1.
Telomeric DNA consists of repetitive G-rich sequences that terminate with a 3΄-ended single stranded overhang (G-tail), which is important for telomere extension by telomerase. Several proteins, including the CST complex, are necessary to maintain telomere structure and length in both yeast and mammals. Emerging evidence indicates that RNA processing factors play critical, yet poorly understood, roles in telomere metabolism. Here, we show that the lack of the RNA processing proteins Xrn1 or Rrp6 partially bypasses the requirement for the CST component Cdc13 in telomere protection by attenuating the activation of the DNA damage checkpoint. Xrn1 is necessary for checkpoint activation upon telomere uncapping because it promotes the generation of single-stranded DNA. Moreover, Xrn1 maintains telomere length by promoting the association of Cdc13 to telomeres independently of ssDNA generation and exerts this function by downregulating the transcript encoding the telomerase inhibitor Rif1. These findings reveal novel roles for RNA processing proteins in the regulation of telomere metabolism with implications for genome stability in eukaryotes.
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan 20126, Italy.
Daniele
D
Cesena
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan 20126, Italy.
Corinne
C
Cassani
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan 20126, Italy.
Emanuela
E
Rizzo
Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
Michael
M
Lisby
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan 20126, Italy.
Diego
D
Bonetti
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan 20126, Italy.
Maria Pia
MP
Longhese
D004277:DNA, Single-Stranded / Q000378:metabolism; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D063326:Exosome Multienzyme Ribonuclease Complex / Q000235:genetics / Q000502:physiology; D009154:Mutation; D012323:RNA Processing, Post-Transcriptional; D012097:Repressor Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016615:Telomere / Q000378:metabolism*; D059505:Telomere Homeostasis; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism; D013696:Temperature
C452219:Cdc13 protein, S cerevisiae; D004277:DNA, Single-Stranded; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D034501:Telomere-Binding Proteins; C074461:RIF1 protein, S cerevisiae; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C068398:XRN1 protein, S cerevisiae; C112610:RRP6 protein, S cerevisiae