Insights from the HuR-interacting transcriptome: ncRNAs, ubiquitin
pathways, and patterns of secondary structure dependent RNA
interactions
Dmitry Babiy, Jianhua Zhou, Ajit Kumar, Silvio Urcuqui-Inchima
Mol Genet Genomics (2012) 287:867–879
Presenter: Yu-Chuan Wu
Commentator: H. Sunny Sun Ph.D
Date/Time: 2013/05/23 17:10-18:00
Location: Room 602, Med College Building
Background:
Hu antigen R (HuR) protein provides a well-annotated model for the study of RNA
binding protein function in signaling pathways and cellular physiology. HuR
influences processing, localization, translation, and the stability of mRNAs
throughout their lifecycle, making important contributions to a coherent set of cellular
functions. HuR can increase target mRNA stability and translation efficiency under
several stress. Although HuR participate in a number of regulation, but the
mechanisms of HuR regulate translation under stress still unclear.
Objective/Hypothesis:
To gain insight into the mechanisms of specificity and sensitivity of HuR’s
interaction with its target RNAs.
Result:
First, the authors used cryogenic immunoprecipitation to pull down Flag-HuR and
Flag-control, then used this sample to perform exon microarray to study HuR
interacting RNAs. They found that the structures in HuR-positive RNAs may
recognize specific fragment which has adenine and uridine bases in a locally less
stable RNA duplex. Using Gene Ontology (GO) analysis, the authors showed
extensive concentration of Ubiquitin Pathway genes among the HuR-positive
transcripts and suggested that HuR not only affect the production of protein but also
regulate the ubiqutin pathways of their selective degradation. In another way, the
authors analyzed the number of natural antisense transcripts associated with HuR.
They further demonstrated that HuR displaces RISC components from target mRNAs
in response to stress and represent a general theme for the mechanism of its
stress-induced regulation of translation. Finally, the authors applied Cluster analysis
and SWORD to provide evidence that HuR’s recognition of its specific RNA targets
composed of primary sequence and secondary structure.
Conclusion:
HuR’s involvement in critical cellular processes depend on its recognition of
secondary structure motifs together with primary sequence in target RNAs. Moreover,
they found HuR could regulate the production of many proteins and the degradation
of many others, suggesting a surprising and coherent duality of biologic function.