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  • Original Paper
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RhoB mRNA is stabilized by HuR after UV light

Oncogene volume 24, pages 502–511 (2005)Cite this article

Abstract

RhoB is a small GTP-binding protein that is involved in apoptotic signal transduction. We have cloned the mouse RhoB mRNA including a 1377 nucleotide 3′-untranslated region (UTR) that contains six AU-rich elements (AREs) as well as several uridine-rich stretches. There is 94% homology overall between the mouse and rat RhoB genes and 92% homology between the mouse and a putative human clone. Ultraviolet light (UVL) induces RhoB production through regulated changes in gene transcription and mRNA stabilization although the latter mechanism is unknown. We observed that UVL increased the half-life of RhoB mRNA from 63 min to 3.3 h in NIH/3T3 cells and from 87 min to 2.7 h in normal human keratinocyte cells. In vitro mobility shift assays demonstrated that HuR bound the 3′-UTR of RhoB at three distinct locations (nucleotides 1342–1696, 1765–1920 and 1897–1977) suggesting a regulatory role for this RNA-binding protein. HuR immunoprecipitations were positive for RhoB mRNA indicating an in vivo association, and Western blot analysis and immunofluorescence demonstrated that HuR rapidly partitions from the nucleus to the cytoplasm after UVL. Therefore, we propose a model in which UVL induces stress-activated signal transduction leading to nuclear/cytoplasmic shuttling of HuR and subsequent stabilization of RhoB mRNA.

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Abbreviations

Act D:

actinomycin D

ARE:

AU-rich element

ERG:

early response gene

EMSA:

electromobility shift assay

ELAV:

embryonic lethal abnormal vision

NHEK:

normal human keratinocyte

PTZ:

pentylenetetrazole

RNP:

ribonucleoprotein

RRM:

RNA recognition motif

UVL:

ultraviolet light

UTR:

untranslated region

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Acknowledgements

We thank Dr Henri Furneaux for pGEX2T/HuR plasmid and anti-HuR antibody (Memorial Sloan-Kettering Cancer Center, New York), Drs Syrus Soltani-nassab and Meggan Czapiga for help with the fluorescence microscopy and members of the laboratory, particularly Amit Dande, for their thoughtful comments. This work was supported by National Institutes of Health Grant RO1 MH61666 (to JSM).

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  1. Virginia B Bartleson

    Present address: Mayo Clinic Medical School, Rochester, MN, USA

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  1. Department of Pathology and Laboratory Medicine, Waisman Center for Developmental Disabilities, University of Wisconsin, Madison, WI, 53705, USA

    Cara J Westmark, Virginia B Bartleson & James S Malter

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Correspondence to James S Malter.

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Westmark, C., Bartleson, V. & Malter, J. RhoB mRNA is stabilized by HuR after UV light. Oncogene 24, 502–511 (2005). https://doi.org/10.1038/sj.onc.1208224

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