MicroRNAs (miRNAs) are an abundant small non-coding RNAs that act as negative gene regulators. Accumulating evidence has suggested that altered miRNA expression plays an essential role in tumorigenesis; however, the molecular mechanisms that lead to the dysregulation of miRNA expression remain elusive.
The research group led by Dr. HUI Jingyi at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, reported the human Y-box binding protein (YB-1) as a new critical regulator of miRNA processing in glioblastoma multiforme (GBM), a class of the most aggressive brain tumor. YB-1 is a major mRNA packaging protein, which plays crucial roles in cancer cell proliferation, transformation, and metastasis in a variety of cancers including GBM, but its key targets are not well characterized.
To search for YB-1 targets, Dr. HUI’s group performed the individual nucleotideresolution crosslinking immunoprecipitation coupled to deep sequencing (iCLIP-seq) experiments and for the first time mapped the in vivo YB-1-RNA interactions at a genome level. They found YB-1 preferentially recognizes a UYAUC consensus motif and binds the majority of coding RNAs. Besides, YB-1 binds extensively to the terminal loop of pri-/pre-miR-29b-2. Using in vivo and in vitro miRNA processing assays, they showed YB-1 inhibits miR-29b-2 processing by blocking the recruitment of the essential miRNA processing factors to the precursors of miRNA. Remarkably, they reported YB-1 promotes cell proliferation through down-regulation of miR-29b in GBM cells.
This work identifies YB-1 as a critical regulator of miRNA expression in GBM, reveals a novel mechanism of YB-1 in the regulation of miRNA processing, and provides new insights into the functional roles of YB-1 during tumorigenesis.
This work entitled “Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme” was published online in Nucleic Acids Research on August 3, 2015. This study was carried out by a graduate student WU Shuailai, Dr. FU Xing, Dr. HUANG Jinyan, and other colleagues under the supervision of Dr. HUI Jingyi, with the help from the Departments of Neurosurgery in the Second Military Medical University and the Sun Yat-sen University, and was supported by the Ministry of Science and Technology of China, the National Natural Science Foundation of China, and the Chinese Academy of Sciences.
CONTACT:
HUI Jingyi, Principal Investigator
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Shanghai 200031, China
Tel: +86-21-5492-1354
E-mail: jyhui@sibcb.ac.cn
Fig. YB-1 inhibits miR-29b-2 processing through binding to its terminal loop region
(Image provided by Prof. HUI Jingyi’s group)
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