Human dyskerin binds to cytoplasmic H/ACA-box-containing transcripts affecting nuclear hormone receptor dependence.
- Resource Type
- Academic Journal
- Authors
- Zacchini F; Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale (DIMES), Alma Mater Studiorum - Università di Bologna, I-40138, Bologna, Italy.; Centro di Ricerca Biomedica Applicata - CRBA, Università̀ di Bologna, Policlinico di Sant'Orsola, I-40138, Bologna, Italy.; Venturi G; Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale (DIMES), Alma Mater Studiorum - Università di Bologna, I-40138, Bologna, Italy.; Centro di Ricerca Biomedica Applicata - CRBA, Università̀ di Bologna, Policlinico di Sant'Orsola, I-40138, Bologna, Italy.; De Sanctis V; Dipartimento di Biologia Cellulare, Computazionale e Integrata (CIBIO), Università di Trento, I-38123, Trento, Italy.; Bertorelli R; Dipartimento di Biologia Cellulare, Computazionale e Integrata (CIBIO), Università di Trento, I-38123, Trento, Italy.; Ceccarelli C; Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale (DIMES), Alma Mater Studiorum - Università di Bologna, I-40138, Bologna, Italy.; Unità Operativa di Anatomia e Istologia Patologica, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, I-40138, Bologna, Italy.; Santini D; Unità Operativa di Anatomia e Istologia Patologica, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, I-40138, Bologna, Italy.; Taffurelli M; Unità Operativa di Chirurgia Senologica, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, I-40138, Bologna, Italy.; Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum - Università di Bologna, I-40138, Bologna, Italy.; Penzo M; Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale (DIMES), Alma Mater Studiorum - Università di Bologna, I-40138, Bologna, Italy.; Centro di Ricerca Biomedica Applicata - CRBA, Università̀ di Bologna, Policlinico di Sant'Orsola, I-40138, Bologna, Italy.; Treré D; Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale (DIMES), Alma Mater Studiorum - Università di Bologna, I-40138, Bologna, Italy.; Departmental Program in Laboratory Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, I-40138, Bologna, Italy.; Inga A; Dipartimento di Biologia Cellulare, Computazionale e Integrata (CIBIO), Università di Trento, I-38123, Trento, Italy.; Dassi E; Dipartimento di Biologia Cellulare, Computazionale e Integrata (CIBIO), Università di Trento, I-38123, Trento, Italy.; Montanaro L; Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale (DIMES), Alma Mater Studiorum - Università di Bologna, I-40138, Bologna, Italy. Lorenzo.montanaro@unibo.it.; Departmental Program in Laboratory Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, I-40138, Bologna, Italy. Lorenzo.montanaro@unibo.it.
- Source
- Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 100960660 Publication Model: Electronic Cited Medium: Internet ISSN: 1474-760X (Electronic) Linking ISSN: 14747596 NLM ISO Abbreviation: Genome Biol Subsets: MEDLINE
- Subject
- Language
- English
Background: Dyskerin is a nuclear protein involved in H/ACA box snoRNA-guided uridine modification of RNA. In humans, its defective function is associated with cancer development and induces specific post-transcriptional alterations of gene expression. In this study, we seek to unbiasedly identify mRNAs regulated by dyskerin in human breast cancer-derived cells.
Results: We find that dyskerin depletion affects the expression and the association with polysomes of selected mRNA isoforms characterized by the retention of H/ACA box snoRNA-containing introns. These snoRNA retaining transcripts (snoRTs) are bound by dyskerin in the cytoplasm in the form of shorter 3' snoRT fragments. We then characterize the whole cytoplasmic dyskerin RNA interactome and find both H/ACA box snoRTs and protein-coding transcripts which may be targeted by the snoRTs' guide properties. Since a fraction of these protein-coding transcripts is involved in the nuclear hormone receptor binding, we test to see if this specific activity is affected by dyskerin. Obtained results indicate that dyskerin dysregulation may alter the dependence on nuclear hormone receptor ligands in breast cancer cells. These results are paralleled by consistent observations on the outcome of primary breast cancer patients stratified according to their tumor hormonal status. Accordingly, experiments in nude mice show that the reduction of dyskerin levels in estrogen-dependent cells favors xenograft development in the absence of estrogen supplementation.
Conclusions: Our work suggests a cytoplasmic function for dyskerin which could affect mRNA post-transcriptional networks relevant for nuclear hormone receptor functions.
(© 2022. The Author(s).)