| http://purl.uniprot.org/citations/36107773 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36107773 | http://www.w3.org/2000/01/rdf-schema#comment | "SERPINA1 mRNAs encode the protease inhibitor α-1-antitrypsin and are regulated through post-transcriptional mechanisms. α-1-antitrypsin deficiency leads to chronic obstructive pulmonary disease (COPD) and liver cirrhosis, and specific variants in the 5'-untranslated region (5'-UTR) are associated with COPD. The NM_000295.4 transcript is well expressed and translated in lung and blood and features an extended 5'-UTR that does not contain a competing upstream open reading frame (uORF). We show that the 5'-UTR of NM_000295.4 folds into a well-defined multi-helix structural domain. We systematically destabilized mRNA structure across the NM_000295.4 5'-UTR, and measured changes in (SHAPE quantified) RNA structure and cap-dependent translation relative to a native-sequence reporter. Surprisingly, despite destabilizing local RNA structure, most mutations either had no effect on or decreased translation. Most structure-destabilizing mutations retained native, global 5'-UTR structure. However, those mutations that disrupted the helix that anchors the 5'-UTR domain yielded three groups of non-native structures. Two of these non-native structure groups refolded to create a stable helix near the translation initiation site that decreases translation. Thus, in contrast to the conventional model that RNA structure in 5'-UTRs primarily inhibits translation, complex folding of the NM_000295.4 5'-UTR creates a translation-optimized message by promoting accessibility at the translation initiation site."xsd:string |
| http://purl.uniprot.org/citations/36107773 | http://purl.org/dc/terms/identifier | "doi:10.1093/nar/gkac739"xsd:string |
| http://purl.uniprot.org/citations/36107773 | http://purl.uniprot.org/core/author | "Lackey L."xsd:string |
| http://purl.uniprot.org/citations/36107773 | http://purl.uniprot.org/core/author | "Weeks K.M."xsd:string |
| http://purl.uniprot.org/citations/36107773 | http://purl.uniprot.org/core/author | "Kumar J."xsd:string |
| http://purl.uniprot.org/citations/36107773 | http://purl.uniprot.org/core/author | "Weidmann C.A."xsd:string |
| http://purl.uniprot.org/citations/36107773 | http://purl.uniprot.org/core/author | "Laederach A."xsd:string |
| http://purl.uniprot.org/citations/36107773 | http://purl.uniprot.org/core/author | "Busan S."xsd:string |
| http://purl.uniprot.org/citations/36107773 | http://purl.uniprot.org/core/author | "Mustoe A.M."xsd:string |
| http://purl.uniprot.org/citations/36107773 | http://purl.uniprot.org/core/author | "Grayeski P.J."xsd:string |
| http://purl.uniprot.org/citations/36107773 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/36107773 | http://purl.uniprot.org/core/name | "Nucleic Acids Res"xsd:string |
| http://purl.uniprot.org/citations/36107773 | http://purl.uniprot.org/core/pages | "9689-9704"xsd:string |
| http://purl.uniprot.org/citations/36107773 | http://purl.uniprot.org/core/title | "Global 5'-UTR RNA structure regulates translation of a SERPINA1 mRNA."xsd:string |
| http://purl.uniprot.org/citations/36107773 | http://purl.uniprot.org/core/volume | "50"xsd:string |
| http://purl.uniprot.org/citations/36107773 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/36107773 |
| http://purl.uniprot.org/citations/36107773 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/36107773 |
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