Structural basis for the activity of a cytoplasmic RNA terminal uridylyl transferase
Cytoplasmic terminal uridylyl transferases comprise a conserved family of enzymes that negatively regulate the stability or biological activity of a variety of eukaryotic RNAs, including mRNAs and tumor-suppressor let-7 microRNAs. Here we describe crystal structures of the Schizosaccharomyces pombe...
| Главные авторы: | , , , , , , |
|---|---|
| Формат: | Journal article |
| Язык: | English |
| Опубликовано: |
2012
|
| _version_ | 1826301838314438656 |
|---|---|
| author | Yates, L Fleurdépine, S Rissland, O De Colibus, L Harlos, K Norbury, C Gilbert, R |
| author_facet | Yates, L Fleurdépine, S Rissland, O De Colibus, L Harlos, K Norbury, C Gilbert, R |
| author_sort | Yates, L |
| collection | OXFORD |
| description | Cytoplasmic terminal uridylyl transferases comprise a conserved family of enzymes that negatively regulate the stability or biological activity of a variety of eukaryotic RNAs, including mRNAs and tumor-suppressor let-7 microRNAs. Here we describe crystal structures of the Schizosaccharomyces pombe cytoplasmic terminal uridylyl transferase Cid1 in two apo conformers and bound to UTP. We demonstrate that a single histidine residue, conserved in mammalian Cid1 orthologs, is responsible for discrimination between UTP and ATP. We also describe a new high-affinity RNA substrate-binding mechanism of Cid1, which is essential for enzymatic activity and is mediated by three basic patches across the surface of the enzyme. Overall, our structures provide a basis for understanding the activity of Cid1 and a mechanism of UTP selectivity conserved in its human orthologs, suggesting potential implications for anticancer drug design. © 2012 Nature America, Inc. All rights reserved. |
| first_indexed | 2024-03-07T05:38:26Z |
| format | Journal article |
| id | oxford-uuid:e4bac1c2-85f8-4dd6-98dc-62ad6b678a0c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:38:26Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:e4bac1c2-85f8-4dd6-98dc-62ad6b678a0c2022-03-27T10:18:42ZStructural basis for the activity of a cytoplasmic RNA terminal uridylyl transferaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e4bac1c2-85f8-4dd6-98dc-62ad6b678a0cEnglishSymplectic Elements at Oxford2012Yates, LFleurdépine, SRissland, ODe Colibus, LHarlos, KNorbury, CGilbert, RCytoplasmic terminal uridylyl transferases comprise a conserved family of enzymes that negatively regulate the stability or biological activity of a variety of eukaryotic RNAs, including mRNAs and tumor-suppressor let-7 microRNAs. Here we describe crystal structures of the Schizosaccharomyces pombe cytoplasmic terminal uridylyl transferase Cid1 in two apo conformers and bound to UTP. We demonstrate that a single histidine residue, conserved in mammalian Cid1 orthologs, is responsible for discrimination between UTP and ATP. We also describe a new high-affinity RNA substrate-binding mechanism of Cid1, which is essential for enzymatic activity and is mediated by three basic patches across the surface of the enzyme. Overall, our structures provide a basis for understanding the activity of Cid1 and a mechanism of UTP selectivity conserved in its human orthologs, suggesting potential implications for anticancer drug design. © 2012 Nature America, Inc. All rights reserved. |
| spellingShingle | Yates, L Fleurdépine, S Rissland, O De Colibus, L Harlos, K Norbury, C Gilbert, R Structural basis for the activity of a cytoplasmic RNA terminal uridylyl transferase |
| title | Structural basis for the activity of a cytoplasmic RNA terminal uridylyl transferase |
| title_full | Structural basis for the activity of a cytoplasmic RNA terminal uridylyl transferase |
| title_fullStr | Structural basis for the activity of a cytoplasmic RNA terminal uridylyl transferase |
| title_full_unstemmed | Structural basis for the activity of a cytoplasmic RNA terminal uridylyl transferase |
| title_short | Structural basis for the activity of a cytoplasmic RNA terminal uridylyl transferase |
| title_sort | structural basis for the activity of a cytoplasmic rna terminal uridylyl transferase |
| work_keys_str_mv | AT yatesl structuralbasisfortheactivityofacytoplasmicrnaterminaluridylyltransferase AT fleurdepines structuralbasisfortheactivityofacytoplasmicrnaterminaluridylyltransferase AT risslando structuralbasisfortheactivityofacytoplasmicrnaterminaluridylyltransferase AT decolibusl structuralbasisfortheactivityofacytoplasmicrnaterminaluridylyltransferase AT harlosk structuralbasisfortheactivityofacytoplasmicrnaterminaluridylyltransferase AT norburyc structuralbasisfortheactivityofacytoplasmicrnaterminaluridylyltransferase AT gilbertr structuralbasisfortheactivityofacytoplasmicrnaterminaluridylyltransferase |