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Journal of Biosciences

, Volume 43, Issue 4, pp 685–691 | Cite as

Posttranscriptional regulation of cyclin D1 by ARE-binding proteins AUF1 and HuR in cycling myoblasts

  • Utpalendu Ghosh
  • Samit Adhya
Article
  • 22 Downloads

Abstract

RNA binding proteins (RBPs) can regulate the stability and/or translatability of messengerRNAs (mRNAs) through interactions with their 3′-untranslated regions. However, individual mRNAs may be regulated simultaneously or successively by more than one RBP, as well as by Argonaute (AGO)-bound miRNAs; the coordination of these various influences on an individual mRNA is therefore complex and not well studied. In this report we examine the roles of two RBPs that bind to AU-rich elements (ARE) – AUF1 and HuR – in the stability and translation of cyclin D1 (Ccnd1) mRNA in rat myoblasts transiting the G phase of the cell cycle, and their interactions with miRNAs. Knockdown (KD) of AUF1 resulted in (1) transient upregulation of the mRNA level as well as an advancement of translation onset time (TOT) from 6 to 5 h post-serum addition, (2) loss of miRNA loading on AGO1 and AGO2 and (3) reduction in the level of AGO-1 and AGO-2 bound mRNA. In contrast, KD of HuR had no effect on the mRNA level, or on the AGO–mRNA complexes, but delayed TOT by 1 h independent of miRNA let-7. Thus the dynamics of RBP–mRNA binding and –RBP–AGO–miRNA interactions are coordinated to fine tune the expression of Ccnd1 in the G1 phase.

Keywords

Argonaute AUF1 cyclin D1 HuR myoblast translation 

Notes

Acknowledgements

This work is supported by the CSIR Emeritus Scientist Scheme. UG received a Senior Research Fellowship from the University Grants Commission.

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Copyright information

© Indian Academy of Sciences 2018

Authors and Affiliations

  1. 1.Molecular Genetics DivisionCSIR-Indian Institute of Chemical BiologyCalcuttaIndia

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