ELAVL1 Modulates Transcriptome-wide miRNA Binding in Murine Macrophages

Lu, Yi-Chien; Chang, Sung-Hee; Hafner, Markus; Li, Xi; Tuschl, Thomas; Elemento, Olivier; Hla, Timothy

doi:10.1016/j.celrep.2014.11.030

Cited by 55 publications

(57 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HuR can also interact with several noncoding (nc)RNAs. It was found to associate with the microRNA let-7, 6,7 although the consequences of this interaction are unclear, and with several long noncoding (lnc)RNAs, including LINCRNAP21, HOTAIR, and RMRP, influencing their stability or subcellular localization. 6,8,9 However, whether or not HuR binds to circular RNAs (circRNAs) and the functional consequences of these interactions have not been studied.…”

Section: Introductionmentioning

confidence: 99%

Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1

et al. 2017

View full text Add to dashboard Cite

HuR influences gene expression programs and hence cellular phenotypes by binding to hundreds of coding and noncoding linear RNAs. However, whether HuR binds to circular RNAs (circRNAs) and impacts on their function is unknown. Here, we have identified en masse circRNAs binding HuR in human cervical carcinoma HeLa cells. One of the most prominent HuR target circRNAs was hsa_circ_0031288, renamed CircPABPN1 as it arises from the PABPN1 pre-mRNA. Further analysis revealed that HuR did not influence CircPABPN1 abundance; interestingly, however, high levels of CircPABPN1 suppressed HuR binding to PABPN1 mRNA. Evaluation of PABPN1 mRNA polysomes indicated that PABPN1 translation was modulated positively by HuR and hence negatively by CircPABPN1. We propose that the extensive binding of CircPABPN1 to HuR prevents HuR binding to PABPN1 mRNA and lowers PABPN1 translation, providing the first example of competition between a circRNA and its cognate mRNA for an RBP that affects translation.

show abstract

Section: Introductionmentioning

confidence: 99%

Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Over the past several years there have been reports of HuR's antagonistic as well as synergistic effect on miR function on a single mRNA (Meisner and Filipowicz 2011;Srikantan et al 2012). However, evidence from transcriptome-wide studies suggests that HuR antagonizes the destabilizing effect of miRs when bound at overlapping binding sites (Mukherjee et al 2011;Lu et al 2014). We found that HuR's binding sites residing within 10 nt of enriched miR target gene sets overlap predicted miR binding sites at frequencies greater than expected (Fig.…”

Section: Utility Of Whole-transcript Analysismentioning

confidence: 76%

“…5B). Given that HuR has been found to generally stabilize mRNA targets while AGO-miR binding is associated with decay of targeted mRNAs, it has been proposed that antagonism of AGO function by HuR may control the turnover of HuR mRNA targets (Mukherjee et al 2011;Lu et al 2014). These results support the conclusion that whole-transcript target analysis using DO-RIP-seq can reveal functionally related RNA targets and, together with binding site information, illuminate the importance of combinatorial relationships among RNA-binding proteins at the binding site level.…”

Section: Do-rip-seq Identifies Enriched Functional Gene Sets and Overmentioning

confidence: 99%

“…Given that HuR can antagonize AGO-miR functions when bound close to AGO-miR binding sites (Mukherjee et al 2011;Lu et al 2014), we used our binding site data to test whether HuR binds within 10 nt of a miR site at frequencies that were greater than that of a shuffled miR set. We selected miR-21, miR-155, and miR-17-5p as candidates whose targets were significantly enriched in HuR DO-RIP-seq, and miR-185, miR-326, and miR-491 as candidates having no significant enrichment in HuR DO-RIP-seq.…”

Section: Do-rip-seq Identifies Enriched Functional Gene Sets and Overmentioning

confidence: 99%

See 1 more Smart Citation

Quantifying RNA binding sites transcriptome-wide using DO-RIP-seq

Nicholson

Friedersdorf

Keene

2016

RNA

View full text Add to dashboard Cite

RNA-binding proteins (RBPs) and noncoding RNAs orchestrate post-transcriptional processes through the recognition of specific sites on targeted transcripts. Thus, understanding the connection between binding to specific sites and active regulation of the whole transcript is essential. Many immunoprecipitation techniques have been developed that identify either whole transcripts or binding sites of RBPs on each transcript using cell lysates. However, none of these methods simultaneously measures the strength of each binding site and quantifies binding to whole transcripts. In this study, we compare current procedures and present digestion optimized (DO)-RIP-seq, a simple method that locates and quantifies RBP binding sites using a continuous metric. We have used the RBP HuR/ELAVL1 to demonstrate that DO-RIP-seq can quantify HuR binding sites with high coverage across the entire human transcriptome, thereby generating metrics of relative RNA binding strength. We demonstrate that this quantitative enrichment of binding sites is proportional to the relative in vitro binding strength for these sites. In addition, we used DO-RIP-seq to quantify and compare HuR's binding to whole transcripts, thus allowing for seamless integration of binding site data with whole-transcript measurements. Finally, we demonstrate that DO-RIP-seq is useful for identifying functional mRNA target sets and binding sites where combinatorial interactions between HuR and AGOmicroRNAs regulate the fate of the transcripts. Our data indicate that DO-RIP-seq will be useful for quantifying RBP binding events that regulate dynamic biological processes.

show abstract

“…HuR is also implicated in gametogenesis, cell differentiation, and stem/progenitor cell survival (Levadoux-Martin et al 2003;Ghosh et al 2009). In macrophages, HuR is involved in the regulation of inflammatory and angiogenic processes (Zhang et al 2012;Lu et al 2014) HuR binds to mRNAs containing AU-rich element (ARE) and U-rich element (URE) (Abdelmohsen and Gorospe 2010). While these sequences are known to be destabilizing for the RNAs that contain them, the binding of HuR and HuD increases the stability of the target mRNAs and sometimes activates their translation (Jain et al 1997).…”

Section: Introductionmentioning

confidence: 99%

RNA-binding protein HuR and the members of the miR-200 family play an unconventional role in the regulation of c-Jun mRNA

Vecchio

Vito

Saunders

et al. 2016

RNA

View full text Add to dashboard Cite

Post-transcriptional gene regulation is a fundamental step for coordinating cellular response in a variety of processes. RNA-binding proteins (RBPs) and microRNAs (miRNAs) are the most important factors responsible for this regulation. Here we report that different components of the miR-200 family are involved in c-Jun mRNA regulation with the opposite effect. While miR-200b inhibits c-Jun protein production, miR-200a tends to increase the JUN amount through a stabilization of its mRNA. This action is dependent on the presence of the RBP HuR that binds the 3 ′ UTR of c-Jun mRNA in a region including the mir-200a binding site. The position of the binding site is fundamental; by mutating this site, we demonstrate that the effect is not micro-RNA specific. These results indicate that miR-200a triggers a microRNA-mediated stabilization of c-Jun mRNA, promoting the binding of HuR with c-Jun mRNA. This is the first example of a positive regulation exerted by a microRNA on an important oncogene in proliferating cells.

show abstract

ELAVL1 Modulates Transcriptome-wide miRNA Binding in Murine Macrophages

Cited by 55 publications

References 56 publications

Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1

Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1

Quantifying RNA binding sites transcriptome-wide using DO-RIP-seq

RNA-binding protein HuR and the members of the miR-200 family play an unconventional role in the regulation of c-Jun mRNA

Contact Info

Product

Resources

About