RNA binding proteins (RBPs) can regulate the stability and/or translatability of messengerRNAs (mRNAs) throughinteractions with their 30-untranslated regions. However, individual mRNAs may be regulated simultaneously or successivelyby more than one RBP, as well as by Argonaute (AGO)-bound miRNAs; the coordination of these various influenceson an individual mRNA is therefore complex and not well studied. In this report we examine the roles of two RBPs thatbind to AU-rich elements (ARE) – AUF1 and HuR – in the stability and translation of cyclin D1 (Ccnd1) mRNA in ratmyoblasts transiting the G phase of the cell cycle, and their interactions with miRNAs. Knockdown (KD) of AUF1 resultedin (1) transient upregulation of the mRNA level as well as an advancement of translation onset time (TOT) from 6 to 5 hpost-serum addition, (2) loss of miRNA loading on AGO1 and AGO2 and (3) reduction in the level of AGO-1 and AGO-2bound mRNA. In contrast, KD of HuR had no effect on the mRNA level, or on the AGO–mRNA complexes, but delayedTOT by 1 h independent of miRNA let-7. Thus the dynamics of RBP–mRNA binding and –RBP–AGO–miRNA interactionsare coordinated to fine tune the expression of Ccnd1 in the G1 phase.
Volume 46, 2021
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