dc.contributor.author | Strand, Elin | |
dc.contributor.author | Hollås, Hanne | |
dc.contributor.author | Sakya, Siri Aastedatter | |
dc.contributor.author | Romanyuk, Sofya | |
dc.contributor.author | Saraste, Mikko Erik Vedeler | |
dc.contributor.author | Grindheim, Ann Kari | |
dc.contributor.author | Patil, Sudarshan S. | |
dc.contributor.author | Vedeler, Anni | |
dc.date.accessioned | 2021-09-30T13:32:10Z | |
dc.date.available | 2021-09-30T13:32:10Z | |
dc.date.created | 2021-08-20T14:06:48Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 1547-6286 | |
dc.identifier.uri | https://hdl.handle.net/11250/2786702 | |
dc.description.abstract | The expression and localization of the oncoprotein c-Myc is highly regulated at the level of transcription, mRNA transport, translation, as well as stability of the protein. We previously showed that Annexin A2 (AnxA2) binds to a specific localization element in the 3ʹuntranslated region (UTR) of c-myc mRNA and is involved in its localization to the perinuclear region. In the present study, we demonstrate that AnxA2 binds in a Ca2+-dependent manner to the internal ribosomal entry site (IRES) containing two pseudo-knots in the 5´UTR of the c-myc mRNA. Here, we employ an in vitro rabbit reticulocyte lysate system with chimeric c-myc reporter mRNAs to demonstrate that binding of AnxA2 to the c-myc IRES modulates the expression of c-Myc. Notably, we show that low levels of AnxA2 appear to increase, while high levels of AnxA2 inhibits translation of the chimeric mRNA. However, when both the AnxA2-binding site and the ribosomal docking site in the c-myc IRES are deleted, AnxA2 has no effect on the translation of the reporter mRNA. Forskolin-treatment of PC12 cells results in upregulation of Ser25 phosphorylated AnxA2 expression while c-Myc expression is down-regulated. The effect of forskolin on c-Myc expression and the level of Ser25 phosphorylated AnxA2 was abolished in the presence of EGTA. These findings indicate that AnxA2 regulates both the transport and subsequent translation of the c-myc mRNA, possibly by silencing the mRNA during its transport. They also suggest that AnxA2 act as a switch to turn off the c-myc IRES activity in the presence of calcium. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Taylor & Francis | en_US |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/deed.no | * |
dc.title | Annexin A2 binds the internal ribosomal entry site of c-myc mRNA and regulates its translation | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2021 the authors | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.doi | 10.1080/15476286.2021.1947648 | |
dc.identifier.cristin | 1927700 | |
dc.source.journal | RNA Biology | en_US |
dc.relation.project | Norges forskningsråd: 240400 | en_US |
dc.identifier.citation | RNA Biology. 2021. | en_US |