LincRNA-p21 Suppresses Target mRNA Translation

Abstract

Mammalian long intergenic noncoding (linc)RNAs are best known for modulating transcription. Here we report a post-transcriptional function for lincRNA-p21 as a modulator of translation. Association of the RNA-binding protein HuR with lincRNA-p21 favored the recruitment of let-7/Ago2 to lincRNA-p21, leading to lower lincRNA-p21 stability. Under reduced HuR levels, lincRNA-p21 accumulated in human cervical carcinoma HeLa cells, increasing its association with JUNB and CTNNB1 mRNAs and selectively lowering their translation. With elevated HuR, lincRNA-p21 levels declined, which in turn derepressed JunB and β-catenin translation and increased the levels of these proteins. We propose that HuR controls translation of a subset of target mRNAs by influencing lincRNA-p21 levels. Our findings uncover a role for lincRNA as a post-transcriptional inhibitor of translation.

H19 Long Noncoding RNA Regulates Intestinal Epithelial Barrier Function via MicroRNA 675 by Interacting with RNA-Binding Protein HuR

“…HuR has three RNA recognition motifs through which it directly interacts with numerous mRNAs to modulate their translation and/or stability (7,36,57). Recent studies revealed that HuR also interacts with several lncRNAs to jointly regulate target transcripts antagonistically or synergistically (7,8,(57)(58)(59)(60). HuR binds lncRNA-p21 and induces the recruitment of let-7/AGO to lncRNA-p21, leading to the destabilization of lncRNA-p21 (7).…”

“…lncRNAs have been involved in a variety of cellular functions, physiologic processes, and disease states by modulating gene expression at different levels, including chromatin remodeling, transcriptional and posttranscriptional control, and protein metabolism (1,3,4). lncRNAs can serve as repressors or activators of gene transcription, as has been extensively reported (1,4), but lncRNAs also can regulate mRNA decay and translation, working jointly with microRNAs (miRNAs) and RNA-binding proteins (RBPs) (7)(8)(9).…”

LncRNAs have a say in protein translation

“…But lncRNAs are probably present at every level of gene regulation. Indeed, recent reports have shown that lncRNAs may also act as molecular decoys for microRNAs [5], inhibit protein translation [6] or control mRNA stability [7]. All the available evidence confirms that the world of lncRNAs is enormously heterogeneous, and the lack of identifiable common features for their functional classification challenges investigators.…”

New insights into the epigenetic control of satellite cells

“…Moreover, increasing evidence indicates that some miRNAs can upregulate gene expression in specific cell types and under certain conditions via the direct action of miRNAs or via the indirect inhibition of repressive miRNA activity [42] . Another class of noncoding RNAs, long noncoding RNAs, has been shown to take part in many transcription regulatory processes [43] and post-transcriptional events, such as mRNA stability and translational control [44][45][46] , and to function as competing endogenous RNA [47][48][49] by acting as an miRNA sponge to participate with coding RNA in a regulatory circuit that controls the binding of RNA to factors such as MyoD, SRF and Myf5 [60] , whose encoded proteins are the primary activators of the myogenic program. Consistent with the notion that H3K4me3 alone does not predict the transcriptional state of a gene but rather marks the gene for transcriptional activation [61] , neither the number nor the identity of genes marked by H3K4me3 is significantly different between activated and quiescent SCs.…”