Integrative regulatory mapping indicates that the RNA-binding protein HuR (ELAVL1) couples pre-mRNA processing and mRNA stability

By Neelanjan Mukherjee, David L. Corcoran, Jeff Nusbaum, David W. Reid, Stoyan Georgiev, M. Hafner, M. Ascano, Thomas Tuschl, Uwe Ohler, Jack D. Keene. Molecules and Cells, 2011

670 citations recorded by the source corpus.

SUMMARY RNA-binding proteins coordinate the fates of multiple RNAs, but the principles underlying these global interactions remain poorly understood. We elucidated regulatory mechanisms of the RNA-binding protein HuR, by integrating data from diverse high-throughput targeting technologies, specifically PAR-CLIP, RIP-chip, and whole-transcript expression profiling. The number of binding sites per transcript, degree of HuR-association, and degree of HuR-dependent RNA stabilization were positively correlated. Pre-mRNA and mature mRNA containing both intronic and 3′ UTR binding sites were more highly stabilized than transcripts with only 3′ UTR or only intronic binding sites, suggesting that HuR couples pre-mRNA processing with mature mRNA stability. We also observed HuR-dependent splicing changes and substantial binding of HuR in poly-pyrimidine tracts of pre-mRNAs. Comparison of the spatial patterns surrounding HuR and miRNA binding sites provided functional evidence for HuR-dependent antagonism of proximal miRNA-mediated repression. We conclude that HuR coordinates gene expression outcomes at multiple interconnected steps of RNA processing.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/589242ca6e9299492d52473c6fa5b93d49a22d90

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Molecular Biology

Citations in the corpus

Regulation of cytoplasmic mRNA decay (2012, neutral): “A recent study using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) to identify HuR-binding sites within the human embryonic kidney cell transcriptome identified 137,305 clusters, 106,840 of which mapped to protein-coding gene”
Long Non-coding RNAs in the Cytoplasm (2016, background): “HuR interacts with many coding and non-coding RNAs, indicating its pleiotropic RNA binding activity [92,93].”
Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1 (2017, background): “3A).(1,2,19) Since CLIP data sets do not distinguish HuR”
A census of human RNA-binding proteins (2014, background): “regulation on a number of mRNA targets (Mukherjee et al., 2011), LIN28 protein competes with the miRNA-processing machinery to suppress pre-let-7 miRNA processing (Cho et al.”
LincRNA-p21 suppresses target mRNA translation. (2012, background): “Recently, photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) analysis (Mukherjee et al., 2011) revealed that the RBP HuR associates with many mRNAs in human cervical carcinoma HeLa cells ( 75% of PAR-CLIP RNA tags), and with numerous ncRNAs ( 25% of tags, identi”
Revealing protein–lncRNA interaction (2015, methodology): “For example, the platform used to detect ELAVL1 RNA interactors [57] is especially rich in”
MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship (2012, background): “Two recent CLIP studies found hundreds of HuR-binding sites that were adjacent to or overlapping with miRNA target sites in unstressed culture cell”