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Cited by 80RNA Research and SplicingNuclear Structure and FunctionDNA Repair Mechanisms

Human Inositol Polyphosphate Multikinase Regulates Transcript-Selective Nuclear MRNA Export to Preserve Genome Integrity

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Wickramasinghe, Vihandha O., Savill, Jane M., Chavali, Sreenivas, Jonsdottir, Asta B., Rajendra, Eeson, Grüner, Tamara, Laskey, Ronald A., Babu, M. Madan +1 more·2013·Molecular Cell
DOI 10.1016/j.molcel.2013.08.031
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Abstract

Messenger RNA (mRNA) export from the nucleus is essential for eukaryotic gene expression. Here we identify a transcript-selective nuclear export mechanism affecting certain human transcripts, enriched for functions in genome duplication and repair, controlled by inositol polyphosphate multikinase (IPMK), an enzyme catalyzing inositol polyphosphate and phosphoinositide turnover. We studied transcripts encoding RAD51, a protein essential for DNA repair by homologous recombination (HR), to characterize the mechanism underlying IPMK-regulated mRNA export. IPMK depletion or catalytic inactivation selectively decreases RAD51 protein abundance and the nuclear export of RAD51 mRNA, thereby impairing HR. Recognition of a sequence motif in the untranslated region of RAD51 transcripts by the mRNA export factor ALY requires IPMK. Phosphatidylinositol (3,4,5)-trisphosphate (PIP3), an IPMK product, restores ALY recognition in IPMK-depleted cell extracts, suggesting a mechanism underlying transcript selection. Our findings implicate IPMK in a transcript-selective mRNA export pathway controlled by phosphoinositide turnover that preserves genome integrity in humans.

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  • IPMK has roles in nutrient sensing, growth factor signaling, mRNA transport, and transcription regulation.

    “Initially identified in yeast and later recognized as essential for mammalian embryonic development, IPMK has transitioned from a niche interest to a focal point in studies of nutrient sensing, growth factor signaling, mRNA transport, and transcription regulation.”

    From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [17]

    The Results and Discussion support a role for human IPMK in mRNA export, and the Introduction describes transcriptional effects of its yeast homolog. The Discussion also reports impaired AKT activation in an IPMK mouse model, but our copy does not establish the broader claims about nutrient sensing or growth factor signaling (searched those terms). (LLM, conf=0.86)

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  • IPMK functions in mRNA export, chromatin remodeling, transcription, nutrient sensing, and growth factor signaling.

    “Its diverse functions span a wide range of cellular processes, including mRNA export [17,18], chromatin remodeling [19,20], transcription [21,22], nutrient sensing [23], and growth factor signaling [15].”

    From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [17]

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Cited by

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Authors
Wickramasinghe, V. O., Savill, J. M., Chavali, S., Jonsdottir, A. B., Rajendra, E., Grüner, T., Laskey, R. A., Babu, M. M., & Venkitaraman, A. R.
Affiliations
  • MRC Cancer Unit (GB)
  • MRC Laboratory of Molecular Biology (GB)
Corresponding author
Venkitaraman, Ashok R.
ORCID
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2013-09
Volume
51
Issue
6
Pages
737-750
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2013.08.031
OpenAlex
W2087826539
Cited by
80
References
6
Citations by year
2026: 3 · 2025: 8 · 2024: 5 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 7 · 2019: 9 · 2018: 8 · 2017: 12 · 2016: 7 · 2015: 10 · 2014: 3
FWCI
2.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
Medical Research Council (MC_UU_12022/8)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords
inositol polyphosphate multikinase, mRNA export, RAD51, homologous recombination, DNA repair, phosphatidylinositol 3,4,5-trisphosphate, phosphoinositide turnover, genome stability, whole-genome duplication
MeSH terms
Cell Nucleus, DNA-Binding Proteins, Humans, Phosphatidylinositols, Phosphorylation, RNA, Messenger, Signal Transduction, Genome, Human, Phosphotransferases (Alcohol Group Acceptor), Phosphatidylinositol 3-Kinases, Active Transport, Cell Nucleus, Genomic Instability, Cell Line, Tumor, Homologous Recombination

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