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Vol. 2. Issue 5.
Pages 217-218 (September - October 2017)
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Vol. 2. Issue 5.
Pages 217-218 (September - October 2017)
PS153
Open Access
HuR prevents c-fos mRNA degradation by proteasome-associated ribonuclease in vitro
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E. Zhigalova1,
Corresponding author
katty_zh@inbox.ru

Corresponding author.
, A. Mittenberg2
1 Skolkovo Institute of Science and Technology, Moscow, Russian Federation
2 Institute of Cytology Russian Academy of Science, St. Petersburg, Russian Federation
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Aim: To estimate HuR protective activity against proteasome-associated ribonuclease for c-myc and c-fos mRNAs.

Introduction: Proteasome-associated proteins are attractive targets for multiple myeloma treatment. One of them is HuR protein known to selectively bind ARE-containing mRNAs and protect them from degradation. HuR is supposed to play a role in cancerogenesis since its expression is elevated in many cancer types and it stabilizes a lot of mRNAs encoding proteins involved in oncogenesis. Previously, it was shown that proteasome in addition to its main function – protein degradation – may act as a selective RNase. Moreover, HuR and proteasome have common targets – c-myc and c-fos protooncogene mRNAs.

Methods: HuR-GST fusion protein has been cloned, expressed and purified by affinity chromatography. Fragments of c-myc and c-fos were cloned and mRNAs have been transcribed in vitro. Proteasomes have been isolated from К562 cell line (human proerytroleykemia) and Im-9 cells (human multiple myeloma). mRNAs were treated by proteasomes in presence and absence of HuR. The estimation of mRNA cleavage was held by gel-electrophoresis.

Results: GST-HuR has specifically bound ARE-containing fragments of c-myc and c-fos mRNAs. Proteasomes extracted from Im-9 and K562 cells cleaved target mRNAs in absence of HuR. It was shown that HuR prevents degradation of c-fos mRNA by proteasomal endoribonuclease, whereas c-myc mRNA was cleaved in the same conditions. GST protein didn’t bind with target mRNAs and didn’t affect proteasome cleavage activity.

Conclusion: HuR protects c-fos mRNA from proteasome ribonuclease cleavage in vitro, but can’t prevent c-myc mRNA degradation. HuR and proteasome compete with each other for manifestation of their opposite activities. Thus, a new mechanism of regulation of proto-oncogenes expression was observed. However, the functional role of this process in vivo should be evaluated in further studies.1–4

References
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S. Srikantan, M. Gorospe.
HuR function in disease.
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M.N. Pouch, F. Petit, J. Buri, Y. Briand, H.P. Schmid.
Identification and initial characterization of a specific proteasome (prosome) associated RNase activity.
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S. Savant-Bhonsale, D.W. Cleveland.
Evidence for instability of mRNAs containing AUUUA motifs mediated through translation-dependent assembly of a > 20S degradation complex.
Genes Dev, 6 (1992), pp. 1927-1939
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