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CLIP: viewing the RNA world from an RNA-protein interactome perspective

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Science China(Life Sciences) 2015年第1期58卷 75-88页

作者： ZHANG Yin XIE ShuJuan XU Hui qu lianghu Key Laboratory of Gene Engineering of Ministry of Education State Key Laboratory for BiocontrolSun Yat-Sen University

The pervasive transcription of the genome creates many types of non-coding RNAs(nc RNAs).However,we know very little regarding the functions and the regulatory mechanisms of these nc *** the interactions of RNA and RNA binding proteins(RBPs) is vital because it can allow us to truly understand how these nc RNAs behave in ***-throughput sequencing of RNA isolated by cross-linking immunoprecipitation(HITS-CLIP or CLIP-seq) and its variants have been successfully used as systemic techniques to study RBP binding *** this review,we will explain the major differences between the CLIP techniques,summarize successful applications of these techniques,discuss limitations of CLIP,present some suggested solutions and project their promising future roles in studying the RNA world.

关键词： CLIP CLASH RPBs nc RNAs functional RNomics

Applications of RNA Indexes for Precision Oncology in Breast Cancer

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Genomics, Proteomics & Bioinformatics 2018年第2期16卷 108-119页

作者： Liming Ma Zirui Liang Hui Zhou lianghu qu Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory of Biocontrol School of Life SciencesSun Yat-sen University

Precision oncology aims to offer the most appropriate treatments to cancer patients mainly based on their individual genetic information. Genomics has provided numerous valuable data on driver mutations and risk loci; however, it remains a formidable challenge to transform these data into therapeutic agents. Transcriptomics describes the multifarious expression patterns of both mRNAs and non-coding RNAs （ncRNAs）, which facilitates the deciphering of genomic codes. In this review, we take breast cancer as an example to demonstrate the applications of these rich RNA resources in precision medicine exploration. These include the use of mRNA profiles in triple-negative breast cancer （TNBC） subtyping to inform corresponding candidate targeted therapies; current advancements and achievements of high-throughput RNA interference （RNAi） screening technologies in breast cancer; and microRNAs as functional signatures for defining cell identities and regulating the biological activities of breast cancer cells. We summarize the benefits of transcriptomic analyses in breast cancer management and propose that unscrambling the core signaling networks of cancer may be an important task of multiple-omic data integration for precision oncology.

关键词： Precision oncology Transcriptomics RNA interference microRNA Breast cancer

Noncoding RNA:from dark matter to bright star

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Science China(Life Sciences) 2020年第4期63卷 463-468页

作者： Yuanchao Xue Runsheng Chen lianghu qu Xiaofeng Cao Key Laboratory of RNA Biology Institute of BiophysicsChinese Academy of SciencesBeijing 100101China MOE Key Laboratory of Gene Function and Regulation State Key Laboratory for BiocontrolSchool of Life SciencesSun Yat-Sen UniversityGuangzhou 510275China State Key Laboratory of Plant Genomics and National Center for Plant Gene Research(Beijing) Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

The central dogma states that genes encoded in the DNA should be first transcribed into messenger RNA(mRNA)and then translated into functional proteins(Crick,1970).This dogma has been written in numerous textbooks and learned by myriad ***,along with the completion of the human genome project in June 2000,an astonishing fact was revealed:only 1.5%of the human genome encodes for proteins(Lander et al.,2001;Venter et al.,2001).This fact raised three fundamental questions:(i)why does the human genome have so few protein-coding genes?(ii)how to explain the apparent differences between humans and other species using the limited coding genes?(iii)what are the roles of the noncoding regions in our genome?

关键词： al. apparent raised

Z3, a novel antisense snoRNA from Saccharomyces cerevisiae

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Chinese Science Bulletin 1998年第7期43卷 586-590页

作者： Yongjun Lu Ling Zhong Hui Zhou Jin Zhao lianghu qu Zhongshan Univ Biotechnol Res Ctr Guangzhou 510275 Peoples R China

Small nucleolar RNA (snoRNA) is one of the most important elements participating in eukaryotic ribosomal biogenesis. The present report describes the results of the identification of a novel snoRNA, Z3, from yeast S. cerevisiae. Z3 snoRNA is 106 nts in length. It contains box C, D elements and a 13 nt complementarity to 25S rRNA. This antisense segment, together with the downstream box D, guides a 2′-O-ribose methylation of cytidine acid at position 2956th in yeast 25 S rRNA. Z3 snoRNA, encoded by an independent transcribed gene on the chromosome  of yeast, possesses the same functional elements responsible for the rRNA methylation site as that of the intron-encoded U35 snoRNA of vertebrate.

关键词： Z3 snoRNA yeast rRNA methylation.

A Helm model for microRNA regulation in cell fate decision and conversion

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Science China(Life Sciences) 2013年第10期56卷 897-906页

作者： XIE ShuJuan ZHANG Yin qu lianghu XU Hui Key Laboratory of Gene Engineering of Ministry of Education State Key Laboratory for BiocontrolSun Yat-sen University

microRNAs （miRNAs） constitute a unique class of endogenous small non-coding RNAs that regulate gene expression post-transcriptionally. Studies over the past decade have uncovered a r^curring paradigm in which miRNAs are key regulators of cellular behavior under various physiological and pathological conditions. Most surprising is the recent observation that miRNAs have emerged as competent players in somatic cell reprogramming, suggesting an especially significant role for these small RNAs in cell fate settings. Here, we discuss the possible mechanisms underlying miRNA-mediated cell programming （i.e., the development and differentiation of embryonic stem cells） and reprogramming （i.e., turning somatic cells into pluripo- tent stem cells or other lineages）, and provide a ＂Helm＂ model of miRNAs in cell fate decision and conversion.

关键词： miRNA(s) cell fate development differentiation embryonic stem cells reprogramming iPS transdifferentiation

Identification of a novel methylated nucleoside in Schizosac-charomyces pombe U6 snRNA

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Chinese Science Bulletin 2000年第14期45卷 1304-1308页

作者： Hui Zhou lianghu qu Yanping Du Weixin Zhou Zhongshan Univ Biotechnol Res Ctr Guangzhou 510275 Peoples R China

By using the method of reverse transcription at different dNTP concentrations, a novel methylated nucleoside, Am64, has been identified from Schizosaccharomyces pombe U6 snRNA, and a higher ordered structure repressin... 详细信息

关键词： Schizosaccharomyces pombe U6 2’ -O-methylation reverse transcription.

The Function of MicroRNAs in Renal Development and Pathophysiology

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Journal of Genetics and Genomics 2013年第4期40卷 143-152页

作者： Liming Ma lianghu qu Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory for BiocontrolSun Yat-sen University

MicroRNAs（miRNAs） are a class of endogenous small non-coding RNAs that modulate diverse biological processes predominantly by translation inhibition or induction of mRNA *** are important regulatory elements involved in renal physiology and *** of miRNAs disrupts early kidney development,renal progenitor cell differentiation and the maintenance of mature *** are also reported to participate in various renal diseases,including chronic kidney disease,acute kidney injury, allograft acute rejection and renal cell *** regulated miRNAs may represent innovative biomarkers for diagnosis and ***,determining the roles of miRNAs in different types of renal diseases will help to clarify the pathogenesis and facilitate the development of novel therapies.

关键词： MicroRNA Renal development Renal pathophysiology

Identification and evolution-ary implication of four novel box H/ACA snoRNAs from Giardia lamblia

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Chinese Science Bulletin 2006年第20期51卷 2451-2456页

作者： LUO Jun ZHOU Hui CHEN Chongjian LI Yan CHEN Yueqin qu lianghu Key Laboratory of Gene Engineering of the Ministry of Education StateKey Laboratory for Biocontrol Zhongshan University Guangzhou510275 China

From a specialized cDNA library, four novel box H/ACA snoRNAs, named GLsR22, GLsR23, GLsR24 and GLsR25, were identified from the primitive eukaryote, Giardia lamblia. Bioinformat- ics analyses indicated that all of them can be poten- tially folded into double hairpins, the typical secon- dary structures of box H/ACA snoRNAs. GLsR24 and GLsR25 are predicted to guide the site-specific pseudouridylation at U1753 and U2396 on 23S rRNA, respectively, while GLsR22 and GLsR23 belong to the family of “orphan” snoRNAs. All of the four novel snoRNAs are encoded by single copy genes and located in small intergenic regions. Interestingly, compared with the counterparts previously reported in Archaea and other unicellular protozoan, the box H/ACA snoRNAs identified from G. lamblia have unique structural features, implying that snoRNAs evolved from prokaryotes to eukaryotes in different ways.

关键词：贾第虫兰氏鞭毛虫基因工程核糖核酸

Cryptotanshinone suppresses key onco-proliferative and drugresistant pathways of chronic myeloid leukemia by targeting STAT5 and STAT3 phosphorylation

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Science China(Life Sciences) 2018年第9期61卷 999-1009页

作者： Bowen Dong Zirui Liang Zhirong Chen Bin Li Lingling Zheng Jianhua Yang Hui Zhou lianghu qu Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory for Biocontrol Sun Yat-sen University

C-Myc and signal transducer and activator of transcription(STAT) family proteins have been proposed to be important downstream genes of BCR-ABL, which characterizes most cases of chronic myeloid leukemia(CML). Here, we report a c-Myc pathway-targeted screening of seven natural anticancer compounds, in which we identified cryptotanshinone as a highly promising agent for CML therapy. Cryptotanshinone depletes c-Myc in CML by repressing the phosphorylation of *** viability of K562 cells correlated with p-STAT5 suppression. Unexpectedly, imatinib activates rather than inhibits the phosphorylation of STAT3 in K562 cells. We demonstrated that cryptotanshinone, as a dual inhibitor of p-STAT5 and p-STAT3,can effectively block IL-6-mediated STAT3 activation and reverse BCR-ABL kinase-independent drug resistance. Moreover, we showed that the epigenetic rebalance between decreased BCR-ABL/STAT5/c-Myc and enhanced STAT3/multi-drug resistance(MDR) pathways is characteristic of the cancer stem cell-like property of K562/ADR. Simultaneously suppressing these two pathways using cryptotanshinone proves to be critical for the malignant network redress and MDR reversal of K562/ADR. These studies reveal the dual functions of cryptotanshinone that suppress key oncogenic proliferation and drug-resistant pathways in CML cells by targeting p-STAT5 and p-STAT3, providing a new strategy for CML therapy that takes advantage of natural products.

关键词： p-STAT3/5 microRNA CML MDR