Jianzhao Liu

Bio: Jianzhao Liu is an academic researcher from Zhejiang University. The author has contributed to research in topics: Medicine & Biology. The author has an hindex of 55, co-authored 111 publications receiving 14266 citations. Previous affiliations of Jianzhao Liu include Life Sciences Institute & University of Chicago.

A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation

Abstract: Certain adenosine residues within mammalian RNAs undergo reversible N6 methylation. Two methyltransferase enzymes, METTL3 and METTL14, as well as the splicing factor WTAP are identified as core components of the multiprotein complex that deposits RNA N6-methyladenosine (m6A) in nuclear RNAs.

Acetylenic polymers: syntheses, structures, and functions.

Abstract: Department of Chemistry, William Mong Institute of Nano Science and Technology, Bioengineering Graduate Program, The Hong Kong University of Science & Technology (HKUST), Clear Water Bay, Kowloon, Hong Kong, China, and Department of Polymer Science and Engineering, Key Laboratory of Macromolecular Synthesis and Functionalization of the Ministry of Education, Institute of Biomedical Macromolecules, Zhejiang University, Hangzhou 310027, China

Twisted Intramolecular Charge Transfer and Aggregation-Induced Emission of BODIPY Derivatives

Abstract: Boron dipyrromethene (BODIPY) derivatives 1 and 2 consisting of donor and acceptor units with dual photoresponses to solvent polarity and luminogen aggregation are developed through taking advantage of twisted intramolecular charge transfer (TICT) and aggregation-induced emission (AIE) processes. In nonpolar solvents, the locally excited (LE) states of the BODIPY luminogens emit intense green lights. Increasing solvent polarity brings the luminogens from the LE state to the TICT state, causing a large bathochromic shift in the emission color but a dramatic decrease in the emission efficiency. The red emission is greatly boosted by aggregate formation or AIE effect: addition of large amounts of water into the solutions of 1 and 2 in the polar solvents causes the luminogens to aggregate supramolecularly and to emit efficiently. The emission can be enhanced by increasing solvent viscosity and decreasing solution temperature, indicating that the AIE effect is caused by the restriction of the intramolecular ro...

RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation

Abstract: Both DNA and histone proteins undergo dynamic and reversible chemical modifications to control gene expression (Strahl and Allis 2000; Bird 2001; Suzuki and Bird 2008; Bhutani et al. 2011; Jones 2012; Kohli and Zhang 2013). Although post-transcriptional modifications are known to occur to RNAs, the impact of these modifications on gene expression regulation has only recently begun to be explored (He 2010). To date, more than a hundred structurally distinct chemical modifications have been found in eukaryotic RNAs (Cantara et al. 2011; Machnicka et al. 2013); however, the enzymes responsible for each modification and the biological consequences of these modified RNAs are largely unknown. RNA modifications were once considered to be static, but a flurry of recent discoveries has demonstrated that some chemical modifications can be dynamic and participate in the regulation of diverse physiological processes (Motorin and Helm 2011; Yi and Pan 2011; Chan et al. 2012; Fu et al. 2014; Meyer and Jaffrey 2014; Kirchner and Ignatova 2015). The presence of N6-methyladenosine (m6A) in polyadenylated mRNA was first discovered in the 1970s (Desrosiers et al. 1974; Perry and Kelley 1974; Lavi and Shatkin 1975; Wei et al. 1975; Schibler et al. 1977; Wei and Moss 1977) by researchers who were characterizing the 5′ cap structure of messenger RNA (mRNA) in mammalian cells. Since then, m6A has been identified as the most prevalent internal modification in mRNA and long noncoding RNA (lncRNA) in higher eukaryotes. It is widely conserved among eukaryotic species that range from yeast, plants, and flies to mammals as well as among viral mRNAs that replicate inside host nuclei (Krug et al. 1976; Beemon and Keith 1977; Horowitz et al. 1984; Bokar 2005). In addition to its occurrence in mRNA, m6A also exists in various classes of RNA in eukaryotes, bacteria, and archaea, including ribosomal RNAs, small nuclear RNAs, and transfer RNAs (Bjork et al. 1987; Maden 1990; Shimba et al. 1995; Gu et al. 1996; Agris et al. 2007; Piekna-Przybylska et al. 2008). Despite its widespread distribution in the mammalian transcriptome (on average, approximately three m6A sites per mRNA), functional insight has been lacking, possibly due to the low abundance of m6A mRNA and technical difficulties in global detection. Interest in the biological relevance of m6A in mRNA resurfaced after the discovery of two mammalian RNA demethylases, FTO (fat mass and obesity-associated protein) (Jia et al. 2011) and its homolog, ALKBH5 (Zheng et al. 2013), which selectively reverse m6A to adenosine in nuclear RNA. FTO is associated with human obesity (Dina et al. 2007; Frayling et al. 2007; Loos and Yeo 2014) and mental development (Hess et al. 2013), while ALKBH5 is shown to affect mouse spermatogenesis in a demethylation-dependent manner (Zheng et al. 2013), suggesting broad roles of m6A in various physiological processes. Shortly after these findings, YTHDF2 (YTH domain-containing family protein 2) was identified as the first m6A reader protein that preferentially recognizes m6A-containing mRNA (Dominissini et al. 2012; Wang et al. 2014a) and mediates mRNA decay (Wang et al. 2014a), thereby suggesting a role for m6A RNA as a negative regulator of gene expression. On the other hand, a transcriptome-wide m6A profiling method was developed to decipher the m6A RNA landscape (Dominissini et al. 2012; Meyer et al. 2012). Intriguingly, m6A sites in mammalian polyadenylated RNA are dominated by the conserved Pu[G > A]m6AC[A/C/U] motif that localizes near stop codons, in 3′ untranslated regions (UTRs), within long internal exons, and at 5′ UTRs (Dominissini et al. 2012; Meyer et al. 2012; Schwartz et al. 2013; Li et al. 2014; Luo et al. 2014), immediately raising the question of how this specificity is achieved. The m6A RNA landscape is initially sculptured by a methyltransferase complex, but for a long time, METTL3 (methyltransferase-like 3) was the only known SAM (S-adenosyl methionine)-binding subunit associated with mRNA methylation (Bokar et al. 1997). In 2014, a new mammalian methyltransferase, METTL14, was discovered to catalyze m6A methylation. Together with METTL3, these two proteins form a stable heterodimer complex that mediates cellular m6A deposition on mammalian mRNAs (Liu et al. 2014; Wang et al. 2014b). Recently, the mammalian splicing factor WTAP (Wilms’ tumor 1-associating protein) was identified as the third auxiliary factor of the core methyltransferase complex that affects cellular m6A methylation (Liu et al. 2014; Ping et al. 2014). The identification and characterization of the complete mammalian m6A methylation machinery are the first steps toward deciphering the selectivity and biological functions of m6A deposition in eukaryotic mRNAs. In this review, we mainly summarize recent progress in the study of m6A methylation in mRNA across different eukaryotes and discuss their newly discovered roles in post-transcriptional gene expression regulation. We first describe the features of m6A on a global scale and briefly introduce the mammalian m6A writers, erasers, and readers that specifically install, remove, or bind to m6A at defined sequence motifs (Fig. 1). We then discuss the evolutional conservation of the m6A methylation machinery across eukaryotic species that range from yeast, plants, and flies to mammals, highlighting the broad roles of methyltransferases and m6A in regulating cell status and embryonic development. Finally, we discuss the emerging functions of m6A in several mechanisms of post-transcriptional gene expression regulation with a special focus on the effects of m6A on differentiation and reprograming of stem cells. Figure 1. Illustration of the cellular pathways of m6A in nuclear RNAs. The m6A methyltransferases and demethylases dynamically control the m6A methylation landscape within the nucleus. The m6A reader proteins preferentially bind to the methylated RNA and mediate ...

Biocompatible Nanoparticles with Aggregation‐Induced Emission Characteristics as Far‐Red/Near‐Infrared Fluorescent Bioprobes for In Vitro and In Vivo Imaging Applications

Abstract: Light emission of 2-(2,6-bis((E)-4-(diphenylamino)styryl)-4H-pyran-4-ylidene)malononitrile (TPA-DCM) is weakened by aggregate formation. Attaching tetraphenylethene (TPE) units as terminals to TPA-DCM dramatically changes its emission behavior: the resulting fluorogen, 2-(2,6-bis((E)-4-(phenyl(4′-(1,2,2-triphenylvinyl)-[1,1′-biphenyl]-4-yl)amino)styryl)-4H-pyran-4-ylidene)malononitrile (TPE-TPA-DCM), is more emissive in the aggregate state, showing the novel phenomenon of aggregation-induced emission (AIE). Formulation of TPE-TPA-DCM using bovine serum albumin (BSA) as the polymer matrix yields uniformly sized protein nanoparticles (NPs) with high brightness and low cytotoxicity. Applications of the fluorogen-loaded BSA NPs for in vitro and in vivo far-red/near-infrared (FR/NIR) bioimaging are successfully demonstrated using MCF-7 breast-cancer cells and a murine hepatoma-22 (H22)-tumor-bearing mouse model, respectively. The AIE-active fluorogen-loaded BSA NPs show an excellent cancer cell uptake and a prominent tumor-targeting ability in vivo due to the enhanced permeability and retention effect.

Aggregation-Induced Emission: Together We Shine, United We Soar!

Abstract: Ju Mei,†,‡,∥ Nelson L. C. Leung,†,‡,∥ Ryan T. K. Kwok,†,‡ Jacky W. Y. Lam,†,‡ and Ben Zhong Tang*,†,‡,§ †HKUST-Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China ‡Department of Chemistry, HKUST Jockey Club Institute for Advanced Study, Institute of Molecular Functional Materials, Division of Biomedical Engineering, State Key Laboratory of Molecular Neuroscience, Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China Guangdong Innovative Research Team, SCUT-HKUST Joint Research Laboratory, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China

Aggregation-induced emission

Abstract: Luminogenic materials with aggregation-induced emission (AIE) attributes have attracted much interest since the debut of the AIE concept in 2001. In this critical review, recent progress in the area of AIE research is summarized. Typical examples of AIE systems are discussed, from which their structure–property relationships are derived. Through mechanistic decipherment of the photophysical processes, structural design strategies for generating new AIE luminogens are developed. Technological, especially optoelectronic and biological, applications of the AIE systems are exemplified to illustrate how the novel AIE effect can be utilized for high-tech innovations (183 references).

Aggregation-Induced Emission: The Whole Is More Brilliant than the Parts

Abstract: "United we stand, divided we fall."--Aesop. Aggregation-induced emission (AIE) refers to a photophysical phenomenon shown by a group of luminogenic materials that are non-emissive when they are dissolved in good solvents as molecules but become highly luminescent when they are clustered in poor solvents or solid state as aggregates. In this Review we summarize the recent progresses made in the area of AIE research. We conduct mechanistic analyses of the AIE processes, unify the restriction of intramolecular motions (RIM) as the main cause for the AIE effects, and derive RIM-based molecular engineering strategies for the design of new AIE luminogens (AIEgens). Typical examples of the newly developed AIEgens and their high-tech applications as optoelectronic materials, chemical sensors and biomedical probes are presented and discussed.