New Insights into Dyskerin-CypA Interaction: Implications for X-Linked Dyskeratosis Congenita and Beyond
The highly conserved family of cyclophilins comprises multifunctional chaperones that interact with proteins and RNAs, facilitating the dynamic assembly of multimolecular complexes involved in various cellular processes. Cyclophilin A (CypA), the predominant member of this family, exhibits peptidyl–...
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MDPI AG
2023-09-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/9/1766 |
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| author | Valentina Belli Daniela Maiello Concetta Di Lorenzo Maria Furia Rosario Vicidomini Mimmo Turano |
| author_facet | Valentina Belli Daniela Maiello Concetta Di Lorenzo Maria Furia Rosario Vicidomini Mimmo Turano |
| author_sort | Valentina Belli |
| collection | DOAJ |
| description | The highly conserved family of cyclophilins comprises multifunctional chaperones that interact with proteins and RNAs, facilitating the dynamic assembly of multimolecular complexes involved in various cellular processes. Cyclophilin A (CypA), the predominant member of this family, exhibits peptidyl–prolyl cis–trans isomerase activity. This enzymatic function aids with the folding and activation of protein structures and often serves as a molecular regulatory switch for large multimolecular complexes, ensuring appropriate inter- and intra-molecular interactions. Here, we investigated the involvement of CypA in the nucleus, where it plays a crucial role in supporting the assembly and trafficking of heterogeneous ribonucleoproteins (RNPs). We reveal that CypA is enriched in the nucleolus, where it colocalizes with the pseudouridine synthase dyskerin, the catalytic component of the multifunctional H/ACA RNPs involved in the modification of cellular RNAs and telomere stability. We show that dyskerin, whose mutations cause the X-linked dyskeratosis (X-DC) and the Hoyeraal–Hreidarsson congenital ribosomopathies, can directly interact with CypA. These findings, together with the remark that substitution of four dyskerin prolines are known to cause X-DC pathogenic mutations, lead us to indicate this protein as a CypA client. The data presented here suggest that this chaperone can modulate dyskerin activity influencing all its partecipated RNPs. |
| first_indexed | 2024-03-10T22:43:55Z |
| format | Article |
| id | doaj.art-fda9c7194b76476789d9a06349b7feb0 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T22:43:55Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-fda9c7194b76476789d9a06349b7feb02023-11-19T10:53:25ZengMDPI AGGenes2073-44252023-09-01149176610.3390/genes14091766New Insights into Dyskerin-CypA Interaction: Implications for X-Linked Dyskeratosis Congenita and BeyondValentina Belli0Daniela Maiello1Concetta Di Lorenzo2Maria Furia3Rosario Vicidomini4Mimmo Turano5Istituto Nazionale Tumori—IRCSS—Fondazione G. Pascale, 80131 Naples, ItalyDepartment of Biology, University of Naples Federico II, 80126 Naples, ItalyDepartment of Biology, University of Naples Federico II, 80126 Naples, ItalyDepartment of Biology, University of Naples Federico II, 80126 Naples, ItalySection on Cellular Communication, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD 20892, USADepartment of Biology, University of Naples Federico II, 80126 Naples, ItalyThe highly conserved family of cyclophilins comprises multifunctional chaperones that interact with proteins and RNAs, facilitating the dynamic assembly of multimolecular complexes involved in various cellular processes. Cyclophilin A (CypA), the predominant member of this family, exhibits peptidyl–prolyl cis–trans isomerase activity. This enzymatic function aids with the folding and activation of protein structures and often serves as a molecular regulatory switch for large multimolecular complexes, ensuring appropriate inter- and intra-molecular interactions. Here, we investigated the involvement of CypA in the nucleus, where it plays a crucial role in supporting the assembly and trafficking of heterogeneous ribonucleoproteins (RNPs). We reveal that CypA is enriched in the nucleolus, where it colocalizes with the pseudouridine synthase dyskerin, the catalytic component of the multifunctional H/ACA RNPs involved in the modification of cellular RNAs and telomere stability. We show that dyskerin, whose mutations cause the X-linked dyskeratosis (X-DC) and the Hoyeraal–Hreidarsson congenital ribosomopathies, can directly interact with CypA. These findings, together with the remark that substitution of four dyskerin prolines are known to cause X-DC pathogenic mutations, lead us to indicate this protein as a CypA client. The data presented here suggest that this chaperone can modulate dyskerin activity influencing all its partecipated RNPs.https://www.mdpi.com/2073-4425/14/9/1766PPIase Aproline isomerizationH/ACA RNPsdyskerinDKC1X-DC |
| spellingShingle | Valentina Belli Daniela Maiello Concetta Di Lorenzo Maria Furia Rosario Vicidomini Mimmo Turano New Insights into Dyskerin-CypA Interaction: Implications for X-Linked Dyskeratosis Congenita and Beyond Genes PPIase A proline isomerization H/ACA RNPs dyskerin DKC1 X-DC |
| title | New Insights into Dyskerin-CypA Interaction: Implications for X-Linked Dyskeratosis Congenita and Beyond |
| title_full | New Insights into Dyskerin-CypA Interaction: Implications for X-Linked Dyskeratosis Congenita and Beyond |
| title_fullStr | New Insights into Dyskerin-CypA Interaction: Implications for X-Linked Dyskeratosis Congenita and Beyond |
| title_full_unstemmed | New Insights into Dyskerin-CypA Interaction: Implications for X-Linked Dyskeratosis Congenita and Beyond |
| title_short | New Insights into Dyskerin-CypA Interaction: Implications for X-Linked Dyskeratosis Congenita and Beyond |
| title_sort | new insights into dyskerin cypa interaction implications for x linked dyskeratosis congenita and beyond |
| topic | PPIase A proline isomerization H/ACA RNPs dyskerin DKC1 X-DC |
| url | https://www.mdpi.com/2073-4425/14/9/1766 |
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