Rhob mrna is stabilized by hur after uv light

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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your

institution Subscribe to this journal Receive 50 print issues and online access $259.00 per year only $5.18 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access

to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our

FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS AGO2 LOCALIZES TO CYTOKINETIC PROTRUSIONS IN A P38-DEPENDENT MANNER AND IS NEEDED FOR ACCURATE CELL DIVISION Article

Open access 11 June 2021 KLF5 AND P53 COMPRISE AN INCOHERENT FEED-FORWARD LOOP DIRECTING CELL-FATE DECISIONS FOLLOWING STRESS Article Open access 02 May 2023 NEGATIVE FEEDBACK REGULATION BY

HUR CONTROLS TRIM21 EXPRESSION AND FUNCTION IN RESPONSE TO UV RADIATION Article Open access 16 July 2020 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 REFERENCES * Adnane J, Muro-Cacho C, Mathews L, Sebti SM and Munoz-Antonia T . (2002). _Clin. Cancer Res._, 8, 2225–2232. *

Anonymous (1998). _Genome Res._, 8, 1097–1108. * Assefa Z, Garmyn M, Bouillon R, Merlevede W, Vandenheede JR and Agostinis P . (1997). _J. Invest. Dermatol._, 108, 886–891. * Blattner C,

Kannouche P, Litfin M, Bender K, Rahmsdorf HJ, Angulo JF and Herrlich P . (2000). _Mol. Cell. Biol._, 20, 3616–3625. * Brook M, Sully G, Clark AR and Saklatvala J . (2000). _FEBS Lett._,

483, 57–61. * Carninci P and Hayashizaki Y . (1999). _Methods Enzymol._, 303, 19–44. * Chen CY, Xu N and Shyu AB . (2002). _Mol. Cell. Biol._, 22, 7268–7278. * Chen W, Tang Q, Gonzales MS

and Bowden GT . (2001). _Oncogene_, 20, 3921–3926. * Chung S, Jiang L, Cheng S and Furneaux H . (1996). _J. Biol. Chem._, 271, 11518–11524. * Delarue FL, Taylor BS and Sebti SM . (2001).

_Oncogene_, 20, 6531–6537. * Dixon DA, Tolley ND, King PH, Nabors LB, McIntyre TM, Zimmerman GA and Prescott SM . (2001). _J. Clin. Invest._, 108, 1657–1665. * Engel ME, Datta PK and Moses

HL . (1998). _J. Biol. Chem._, 273, 9921–9926. * Fan XC and Steitz JA . (1998a). _Proc. Natl. Acad. Sci. USA_, 95, 15293–15298. * Fan XC and Steitz JA . (1998b). _EMBO J._, 17, 3448–3460. *

Fritz G, Gnad R and Kaina B . (1999). _Anticancer Res._, 19, 1681–1688. * Fritz G and Kaina B . (2000). _Biochem. Biophys. Res. Commun._, 268, 784–789. * Fritz G and Kaina B . (2001a). _J.

Biol. Chem._, 276, 3115–3122. * Fritz G and Kaina B . (2001b). _Nucleic Acids Res._, 29, 792–798. * Fritz G, Kaina B and Aktories K . (1995). _J. Biol. Chem._, 270, 25172–25177. * Gallouzi

IE, Brennan CM and Steitz JA . (2001). _RNA_, 7, 1348–1361. * Gallouzi IE, Brennan CM, Stenberg MG, Swanson MS, Eversole A, Maizels N and Steitz JA . (2000). _Proc. Natl. Acad. Sci. USA_,

97, 3073–3078. * Gampel A, Parker PJ and Mellor H . (1999). _Curr. Biol._, 9, 955–958. * Giles KM, Daly JM, Beveridge DJ, Thomson AM, Voon DC, Furneaux HM, Jazayeri JA and Leedman PJ .

(2003). _J. Biol. Chem._, 278, 2937–2946. * Hernandez-Perera O, Perez-Sala D, Soria E and Lamas S . (2000). _Circ. Res._, 87, 616–622. * Jahner D and Hunter T . (1991). _Mol. Cell. Biol._,

11, 3682–3690. * Jiang K, Delarue FL and Sebti SM . (2004a). _Oncogene_, 23, 1136–1145. * Jiang K, Sun J, Cheng J, Djeu JY, Wei S and Sebti S . (2004b). _Mol. Cell. Biol._, 24, 5565–5576. *

Kasashima K, Sakashita E, Saito K and Sakamoto H . (2002). _Nucleic Acids Res._, 30, 4519–4526. * Kirigiti P, Bai Y, Yang YF, Li X, Li B, Brewer G and Machida CA . (2001). _Mol. Pharmacol._,

60, 1308–1324. * Koike K, Uchiumi T, Ohga T, Toh S, Wada M, Kohno K and Kuwano M . (1997). _FEBS Lett._, 417, 390–394. * Lagnado CA, Brown CY and Goodall GJ . (1994). _Mol. Cell. Biol._,

14, 7984–7995. * Lal A, Mazan-Mamczarz K, Kawai T, Yang X, Martindale JL and Gorospe M . (2004). _EMBO J._, 23, 3092–3102. * Lasa M, Mahtani KR, Finch A, Brewer G, Saklatvala J and Clark AR

. (2000). _Mol. Cell. Biol._, 20, 4265–4274. * Levy NS, Chung S, Furneaux H and Levy AP . (1998). _J. Biol. Chem._, 273, 6417–6423. * Liu AX, Rane N, Liu JP and Prendergast GC . (2001).

_Mol. Cell. Biol._, 21, 6906–6912. * Lopez de Silanes I, Zhan M, Lal A, Yang X and Gorospe M . (2004). _Proc. Natl. Acad. Sci. USA_, 101, 2987–2992. * Ma WJ, Cheng S, Campbell C, Wright A

and Furneaux H . (1996). _J. Biol. Chem._, 271, 8144–8151. * Ma WJ, Chung S and Furneaux H . (1997). _Nucleic Acids Res._, 25, 3564–3569. * Malcolm T, Ettehadieh E and Sadowski I . (2003).

_Oncogene_, 22, 6142–6150. * Maurer F, Tierney M and Medcalf RL . (1999). _Nucleic Acids Res._, 27, 1664–1673. * Mazieres J, Antonia T, Daste G, Muro-Cacho C, Berchery D, Tillement V,

Pradines A, Sebti S and Favre G . (2004). _Clin. Cancer Res._, 10, 2742–2750. * Mellor H, Flynn P, Nobes CD, Hall A and Parker PJ . (1998). _J. Biol. Chem._, 273, 4811–4814. * Miyakawa Y and

Matsushime H . (2001). _Biochem. Biophys. Res. Commun._, 284, 71–76. * Montero L and Nagamine Y . (1999). _Cancer Res._, 59, 5286–5293. * Nakamura T, Asano M, Shindo-Okada N, Nishimura S

and Monden Y . (1996). _Biochem. Biophys. Res. Commun._, 226, 688–694. * Park-Lee S, Kim S and Laird-Offringa IA . (2003). _J. Biol. Chem._, 278, 39801–39808. * Peng SS, Chen CY, Xu N and

Shyu AB . (1998). _EMBO J._, 17, 3461–3470. * Pillaire MJ, Nebreda AR and Darbon JM . (2000). _Biochem. Biophys. Res. Commun._, 278, 724–728. * Prendergast GC, Khosravi-Far R, Solski PA,

Kurzawa H, Lebowitz PF and Der CJ . (1995). _Oncogene_, 10, 2289–2296. * Schaeffer HJ and Weber MJ . (1999). _Mol. Cell. Biol._, 19, 2435–2444. * Shao J, Sheng H, Inoue H, Morrow JD and

DuBois RN . (2000). _J. Biol. Chem._, 275, 33951–33956. * Takai Y, Sasaki T and Matozaki T . (2001). _Physiol. Rev._, 81, 153–208. * Tran H, Maurer F and Nagamine Y . (2003). _Mol. Cell.

Biol._, 23, 7177–7188. * Trapp T, Korhonen L, Besselmann M, Martinez R, Mercer EA and Lindholm D . (2003). _Mol. Cell. Neurosci._, 23, 302–313. * Trapp T, Olah L, Holker I, Besselmann M,

Tiesler C, Maeda K and Hossmann KA . (2001). _Mol. Cell. Neurosci._, 17, 883–894. * van der Houven van Oordt W, Diaz-Meco MT, Lozano J, Krainer AR, Moscat J and Caceres JF . (2000). _J. Cell

Biol._, 149, 307–316. * Wang W, Caldwell MC, Lin S, Furneaux H and Gorospe M . (2000a). _EMBO J._, 19, 2340–2350. * Wang W, Furneaux H, Cheng H, Caldwell MC, Hutter D, Liu Y, Holbrook N and

Gorospe M . (2000b). _Mol. Cell. Biol._, 20, 760–769. * Wennerberg K and Der CJ . (2004). _J. Cell Sci._, 117, 1301–1312. * Westmark CJ and Malter JS . (2001a). _Brain. Res. Mol. Brain

Res._, 90, 193–201. * Westmark CJ and Malter JS . (2001b). _J. Biol. Chem._, 276, 1119–1126. * Winzen R, Kracht M, Ritter B, Wilhelm A, Chen CY, Shyu AB, Muller M, Gaestel M, Resch K and

Holtmann H . (1999). _EMBO J._, 18, 4969–4980. * Yang C and Carrier F . (2001). _J. Biol. Chem._, 276, 47277–47284. Download references 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). AUTHOR INFORMATION Author

notes * Virginia B Bartleson Present address: Mayo Clinic Medical School, Rochester, MN, USA AUTHORS AND AFFILIATIONS * 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 Authors * Cara J Westmark View author publications You

can also search for this author inPubMed Google Scholar * Virginia B Bartleson View author publications You can also search for this author inPubMed Google Scholar * James S Malter View

author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to James S Malter. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT

THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 19 August 2004 * Revised: 21 September 2004 * Accepted: 25 September 2004 * Published: 15 November 2004 * Issue Date: 13

January 2005 * DOI: https://doi.org/10.1038/sj.onc.1208224 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a

shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * RhoB * HuR * ARE * mRNA stability

* UVL