Enhanced translation by Nucleolin via G-rich elements in coding and non-coding regions of target mRNAs

Abstract

RNA-binding proteins (RBPs) regulate gene expression at many post-transcriptional levels, including mRNA stability and translation. The RBP nucleolin, with four RNA-recognition motifs, has been implicated in cell proliferation, carcinogenesis and viral infection. However, the subset of nucleolin target mRNAs and the influence of nucleolin on their expression had not been studied at a transcriptome-wide level. Here, we globally identified nucleolin target transcripts, many of which encoded cell growth- and cancer-related proteins, and used them to find a signature motif on nucleolin target mRNAs. Surprisingly, this motif was very rich in G residues and was not only found in the 3′-untranslated region (UTR), but also in the coding region (CR) and 5′-UTR. Nucleolin enhanced the translation of mRNAs bearing the G-rich motif, since silencing nucleolin did not change target mRNA stability, but decreased the size of polysomes forming on target transcripts and lowered the abundance of the encoded proteins. In summary, nucleolin binds G-rich sequences in the CR and UTRs of target mRNAs, many of which encode cancer proteins, and enhances their translation.

Nucleolin mediated pro‐angiogenic role of Hydroxysafflor Yellow A in ischaemic cardiac dysfunction: Post‐transcriptional regulation of VEGF‐A and MMP‐9

“…Cell surface nucleolin is even proved to be a specific marker of angiogenic endothelial cells in the vasculature 39. Moreover, nucleolin displayed remarkably cardioprotective, antiapoptotic and tumour inhibitory effects, etc 18, 23, 40, 41. In the present study, we found that HSYA dominantly increased the nucleolin expression in the ischaemic myocardium and HUVECs.…”

Transformer 2β and miR-204 regulate apoptosis through competitive binding to 3′ UTR of BCL2 mRNA

“…29 Several RNA-binding proteins (HuR, nuclear factor 90, tristetraprolin, butyrate response factor 1, and K homology-type splicing regulatory protein) preferentially interact with U/AU-rich sequences in the 3′ UTR of the target transcripts and regulate their stability, whereas nucleolin preferentially binds to G-rich sequences. 30 SR proteins also participate in the regulation of mRNA turnover. For example, SRSF1 selectively enhances the decay of target mRNAs by binding to their 3′ UTRs.…”

RNA-binding protein nucleolin in disease

“…Many of nucleolin target mRNAs bear AU-rich elements (AREs), typically present in their 3'-untranslated region (UTR), and/or G-rich sequences distributed in the 5' UTR, coding region (CR), and 3' UTR. 13,32 In this section, we will discuss those nucleolin target mRNAs which are best characterized, and we will highlight the impact of the encoded proteins in disease processes ( Table 1).…”

“…12 The central region of nucleolin contains four RNA-recognition motifs (RRMs) and mediates the interaction with mRNAs and pre-rRNA. 13,14 The C-terminal region of nucleolin contains an arginine/glycine-rich domain (RGG), through which nucleolin can interact with target mRNAs as well as with other proteins, including ribosomal proteins. 13,15,16 Nucleolin has been extensively implicated in DNA metabolism.…”

“…13,14 The C-terminal region of nucleolin contains an arginine/glycine-rich domain (RGG), through which nucleolin can interact with target mRNAs as well as with other proteins, including ribosomal proteins. 13,15,16 Nucleolin has been extensively implicated in DNA metabolism. It affects DNA replication, telomere maintenance and DNA repair, and recombination.…”