JKTBP1 is involved in stabilization and IRES-dependent translation of NRF mRNAs by binding to 5' and 3' untranslated regions.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620803
Title:
JKTBP1 is involved in stabilization and IRES-dependent translation of NRF mRNAs by binding to 5' and 3' untranslated regions.
Authors:
Omnus, Deike Johanne; Mehrtens, Sarah; Ritter, Birgit; Resch, Klaus; Yamada, Michiyuki; Frank, Ronald; Nourbakhsh, Mahtab; Reboll, Marc René
Abstract:
Heterogeneous nuclear ribonucleoprotein D-like protein (JKTBP) 1 was implicated in cap-independent translation by binding to the internal ribosome entry site in the 5' untranslated region (UTR) of NF-κB-repressing factor (NRF). Two different NRF mRNAs have been identified so far, both sharing the common 5' internal ribosome entry site but having different length of 3' UTRs. Here, we used a series of DNA and RNA luciferase reporter constructs comprising 5', 3' or both NRF UTRs to study the effect of JKTBP1 on translation of NRF mRNA variants. The results indicate that JKTBP1 regulates the level of NRF protein expression by binding to both NRF 5' and 3' UTRs. Using successive deletion and point mutations as well as RNA binding studies, we define two distinct JKTBP1 binding elements in NRF 5' and 3' UTRs. Furthermore, JKTBP1 requires two distinct RNA binding domains to interact with NRF UTRs and a short C-terminal region for its effect on NRF expression. Together, our study shows that JKTBP1 contributes to NRF protein expression via two disparate mechanisms: mRNA stabilization and cap-independent translation. By binding to 5' UTR, JKTBP1 increases the internal translation initiation in both NRF mRNA variants, whereas its binding to 3' UTR elevated primarily the stability of the major NRF mRNA. Thus, JKTBP1 is a key regulatory factor linking two pivotal control mechanisms of NRF gene expression: the cap-independent translation initiation and mRNA stabilization.
Affiliation:
Helmholtz Centre for infection research. Inhoffenstr. 7. 38124 Braunschweig, Germany.
Citation:
JKTBP1 is involved in stabilization and IRES-dependent translation of NRF mRNAs by binding to 5' and 3' untranslated regions. 2011, 407 (4):492-504 J. Mol. Biol.
Journal:
Journal of molecular biology
Issue Date:
8-Apr-2011
URI:
http://hdl.handle.net/10033/620803
DOI:
10.1016/j.jmb.2011.01.050
PubMed ID:
21300069
Type:
Article
Language:
en
ISSN:
1089-8638
Appears in Collections:
Publications of the research group Chemical Biology (CBIO)

Full metadata record

DC FieldValue Language
dc.contributor.authorOmnus, Deike Johanneen
dc.contributor.authorMehrtens, Sarahen
dc.contributor.authorRitter, Birgiten
dc.contributor.authorResch, Klausen
dc.contributor.authorYamada, Michiyukien
dc.contributor.authorFrank, Ronalden
dc.contributor.authorNourbakhsh, Mahtaben
dc.contributor.authorReboll, Marc Renéen
dc.date.accessioned2017-02-02T15:36:16Z-
dc.date.available2017-02-02T15:36:16Z-
dc.date.issued2011-04-08-
dc.identifier.citationJKTBP1 is involved in stabilization and IRES-dependent translation of NRF mRNAs by binding to 5' and 3' untranslated regions. 2011, 407 (4):492-504 J. Mol. Biol.en
dc.identifier.issn1089-8638-
dc.identifier.pmid21300069-
dc.identifier.doi10.1016/j.jmb.2011.01.050-
dc.identifier.urihttp://hdl.handle.net/10033/620803-
dc.description.abstractHeterogeneous nuclear ribonucleoprotein D-like protein (JKTBP) 1 was implicated in cap-independent translation by binding to the internal ribosome entry site in the 5' untranslated region (UTR) of NF-κB-repressing factor (NRF). Two different NRF mRNAs have been identified so far, both sharing the common 5' internal ribosome entry site but having different length of 3' UTRs. Here, we used a series of DNA and RNA luciferase reporter constructs comprising 5', 3' or both NRF UTRs to study the effect of JKTBP1 on translation of NRF mRNA variants. The results indicate that JKTBP1 regulates the level of NRF protein expression by binding to both NRF 5' and 3' UTRs. Using successive deletion and point mutations as well as RNA binding studies, we define two distinct JKTBP1 binding elements in NRF 5' and 3' UTRs. Furthermore, JKTBP1 requires two distinct RNA binding domains to interact with NRF UTRs and a short C-terminal region for its effect on NRF expression. Together, our study shows that JKTBP1 contributes to NRF protein expression via two disparate mechanisms: mRNA stabilization and cap-independent translation. By binding to 5' UTR, JKTBP1 increases the internal translation initiation in both NRF mRNA variants, whereas its binding to 3' UTR elevated primarily the stability of the major NRF mRNA. Thus, JKTBP1 is a key regulatory factor linking two pivotal control mechanisms of NRF gene expression: the cap-independent translation initiation and mRNA stabilization.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.mesh3' Untranslated Regionsen
dc.subject.mesh5' Untranslated Regionsen
dc.subject.meshArtificial Gene Fusionen
dc.subject.meshGenes, Reporteren
dc.subject.meshLuciferasesen
dc.subject.meshPoint Mutationen
dc.subject.meshProtein Bindingen
dc.subject.meshProtein Biosynthesisen
dc.subject.meshRNA Stabilityen
dc.subject.meshRNA, Messengeren
dc.subject.meshRNA-Binding Proteinsen
dc.subject.meshRepressor Proteinsen
dc.subject.meshRibonucleoproteinsen
dc.subject.meshSequence Deletionen
dc.titleJKTBP1 is involved in stabilization and IRES-dependent translation of NRF mRNAs by binding to 5' and 3' untranslated regions.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research. Inhoffenstr. 7. 38124 Braunschweig, Germany.en
dc.identifier.journalJournal of molecular biologyen

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