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Full-length NF-κB repressing factor contains an XRN2 binding domain

NF-κB repressing factor (NKRF) was recently identified as an RNA binding protein that together with its associated proteins, the 5′–3′ exonuclease XRN2 and the helicase DHX15, is required to process the precursor ribosomal RNA. XRN2 is a multi-functional ribonuclease that is also involved in process...

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Autores principales: Alexandrova, Jana, Piñeiro, David, Jukes-Jones, Rebekah, Mordue, Ryan, Stoneley, Mark, Willis, Anne E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054742/
https://www.ncbi.nlm.nih.gov/pubmed/32011671
http://dx.doi.org/10.1042/BCJ20190733
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author Alexandrova, Jana
Piñeiro, David
Jukes-Jones, Rebekah
Mordue, Ryan
Stoneley, Mark
Willis, Anne E.
author_facet Alexandrova, Jana
Piñeiro, David
Jukes-Jones, Rebekah
Mordue, Ryan
Stoneley, Mark
Willis, Anne E.
author_sort Alexandrova, Jana
collection PubMed
description NF-κB repressing factor (NKRF) was recently identified as an RNA binding protein that together with its associated proteins, the 5′–3′ exonuclease XRN2 and the helicase DHX15, is required to process the precursor ribosomal RNA. XRN2 is a multi-functional ribonuclease that is also involved in processing mRNAs, tRNAs and lncRNAs. The activity and stability of XRN2 are controlled by its binding partners, PAXT-1, CDKN2AIP and CDKN2AIPNL. In each case, these proteins interact with XRN2 via an XRN2 binding domain (XTBD), the structure and mode of action of which is highly conserved. Rather surprisingly, although NKRF interacts directly with XRN2, it was not predicted to contain such a domain, and NKRF's interaction with XRN2 was therefore unexplained. We have identified an alternative upstream AUG start codon within the transcript that encodes NKRF and demonstrate that the full-length form of NKRF contains an XTBD that is conserved across species. Our data suggest that NKRF is tethered in the nucleolus by binding directly to rRNA and that the XTBD in the N-terminal extension of NKRF is essential for the retention of XRN2 in this sub-organelle. Thus, we propose NKRF regulates the early steps of pre-rRNA processing during ribosome biogenesis by controlling the spatial distribution of XRN2 and our data provide further support for the XTBD as an XRN2 interacting motif.
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spelling pubmed-70547422020-03-11 Full-length NF-κB repressing factor contains an XRN2 binding domain Alexandrova, Jana Piñeiro, David Jukes-Jones, Rebekah Mordue, Ryan Stoneley, Mark Willis, Anne E. Biochem J Gene Expression & Regulation NF-κB repressing factor (NKRF) was recently identified as an RNA binding protein that together with its associated proteins, the 5′–3′ exonuclease XRN2 and the helicase DHX15, is required to process the precursor ribosomal RNA. XRN2 is a multi-functional ribonuclease that is also involved in processing mRNAs, tRNAs and lncRNAs. The activity and stability of XRN2 are controlled by its binding partners, PAXT-1, CDKN2AIP and CDKN2AIPNL. In each case, these proteins interact with XRN2 via an XRN2 binding domain (XTBD), the structure and mode of action of which is highly conserved. Rather surprisingly, although NKRF interacts directly with XRN2, it was not predicted to contain such a domain, and NKRF's interaction with XRN2 was therefore unexplained. We have identified an alternative upstream AUG start codon within the transcript that encodes NKRF and demonstrate that the full-length form of NKRF contains an XTBD that is conserved across species. Our data suggest that NKRF is tethered in the nucleolus by binding directly to rRNA and that the XTBD in the N-terminal extension of NKRF is essential for the retention of XRN2 in this sub-organelle. Thus, we propose NKRF regulates the early steps of pre-rRNA processing during ribosome biogenesis by controlling the spatial distribution of XRN2 and our data provide further support for the XTBD as an XRN2 interacting motif. Portland Press Ltd. 2020-02-28 2020-02-27 /pmc/articles/PMC7054742/ /pubmed/32011671 http://dx.doi.org/10.1042/BCJ20190733 Text en © 2020 The Author(s) https://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . Open access for this article was enabled by the participation of University of Cambridge in an all-inclusive Read & Publish pilot with Portland Press and the Biochemical Society under a transformative agreement with JISC.
spellingShingle Gene Expression & Regulation
Alexandrova, Jana
Piñeiro, David
Jukes-Jones, Rebekah
Mordue, Ryan
Stoneley, Mark
Willis, Anne E.
Full-length NF-κB repressing factor contains an XRN2 binding domain
title Full-length NF-κB repressing factor contains an XRN2 binding domain
title_full Full-length NF-κB repressing factor contains an XRN2 binding domain
title_fullStr Full-length NF-κB repressing factor contains an XRN2 binding domain
title_full_unstemmed Full-length NF-κB repressing factor contains an XRN2 binding domain
title_short Full-length NF-κB repressing factor contains an XRN2 binding domain
title_sort full-length nf-κb repressing factor contains an xrn2 binding domain
topic Gene Expression & Regulation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054742/
https://www.ncbi.nlm.nih.gov/pubmed/32011671
http://dx.doi.org/10.1042/BCJ20190733
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