2011 Vol. 2, No. 9

News and views
Ageing in worms: N-acylethanolamines take control
Run Shen
2011, 2(9): 689-690. doi: 10.1007/s13238-011-1099-x
Biotin biosynthesis in Mycobacterium tuberculosis: physiology, biochemistry and molecular intervention
Wanisa Salaemae, Al Azhar, Grant W. Booker, Steven W. Polyak
2011, 2(9): 691-695. doi: 10.1007/s13238-011-1100-8
A successful international cooperation with a bumpy start
Ming Li
2011, 2(9): 696-698. doi: 10.1007/s13238-011-1103-5
CUEDC2: an emerging key player in inflammation and tumorigenesis
Jianghong Man, Xuemin Zhang
2011, 2(9): 699-703. doi: 10.1007/s13238-011-1089-z
CUE domain-containing 2 (CUEDC2) is a protein involved in the regulation of the cell cycle, inflammation, and tumorigenesis and is highly expressed in many types of tumors. CUEDC2 is phosphorylated by Cdk1 during mitosis and promotes the release of anaphase-promoting complex or cyclosome (APC/C) from checkpoint inhibition. CUEDC2 is also known to interact with IkB kinase α (IKKα) and IKKβ and has an inhibitory role in the activation of transcription factor nuclear factor-κB. Moreover, CUEDC2 plays an important role in downregulating the expression of hormone receptors estrogen receptor-α and progesterone receptor, thereby impairing the responsiveness of breast cancer to endocrine therapies. In this review, current knowledge on the multi-functions of CUEDC2 in normal processes and tumorigenesis are discussed and summarized.
The Fanconi anemia pathway and DNA interstrand cross-link repair
Xiaoyu Su, Jun Huang
2011, 2(9): 704-711. doi: 10.1007/s13238-011-1098-y
Fanconi anemia (FA) is an autosomal or X-linked recessive disorder characterized by chromosomal instability, bone marrow failure, cancer susceptibility, and a profound sensitivity to agents that produce DNA interstrand cross-link (ICL). To date, 15 genes have been identified that, when mutated, result in FA or an FA-like syndrome. It is believed that cellular resistance to DNA interstrand cross-linking agents requires all 15 FA or FAlike proteins. Here, we review our current understanding of how these FA proteins participate in ICL repair and discuss the molecular mechanisms that regulate the FA pathway to maintain genome stability.
Pseudouridines in spliceosomal snRNAs
Andrew T. Yu, Junhui Ge, Yi-Tao Yu
2011, 2(9): 712-725. doi: 10.1007/s13238-011-1087-1
Spliceosomal RNAs are a family of small nuclear RNAs (snRNAs) that are essential for pre-mRNA splicing. All vertebrate spliceosomal snRNAs are extensively pseudouridylated after transcription. Pseudouridines in spliceosomal snRNAs are generally clustered in regions that are functionally important during splicing. Many of these modified nucleotides are conserved across species lines. Recent studies have demonstrated that spliceosomal snRNA pseudouridylation is catalyzed by two different mechanisms:an RNA-dependent mechanism and an RNA-independent mechanism. The functions of the pseudouridines in spliceosomal snRNAs (U2 snRNA in particular) have also been extensively studied. Experimental data indicate that virtually all pseudouridines in U2 snRNA are functionally important. Besides the currently known pseudouridines (constitutive modifications), recent work has also indicated that pseudouridylation can be induced at novel positions under stress conditions, thus strongly suggesting that pseudouridylation is also a regulatory modification.
Molecular regulation of telomerase activity in aging
Craig Nicholls, He Li, Jian-Qiu Wang, Jun-Ping Liu
2011, 2(9): 726-738. doi: 10.1007/s13238-011-1093-3
The process of aging is mitigated by the maintenance and repair of chromosome ends (telomeres), resulting in extended lifespan. This review examines the molecular mechanisms underlying the actions and regulation of the enzyme telomerase reverse transcriptase (TERT), which functions as the primary mechanism of telomere maintenance and regulates cellular life expectancy. Underpinning increased cell proliferation, telomerase is also a key factor in facilitating cancer cell immortalization. The review focuses on aspects of hormonal regulations of telomerase, and the intracellular pathways that converge to regulate telomerase activity with an emphasis on molecular interactions at protein and gene levels. In addition, the basic structure and function of two key telomerase enzyme components-the catalytic subunit TERT and the template RNA (TERC) are discussed briefly.
Elevated levels of serum antibodies against alpha-1, 6-glucan in patients with systemic lupus erythematosus or rheumatoid arthritis
Hui Dai, Xiao-Ming Gao
2011, 2(9): 739-744. doi: 10.1007/s13238-011-1095-1
This study was undertaken to investigate whether levels of anti-alpha-1, 6-glucan antibodies in human sera correlate with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Serum samples were collected from patients with SLE (n=30), RA (n=30) and healthy adult volunteers. IgG, IgA and IgM levels against alpha-1, 6-glucan were measured using enzyme linked immunosorbent assays. Anti-alpha-1, 6-glucan IgG prevalence was raised in patients with active SLE (73.3%) and RA (60%) compared with healthy controls (13.3%). Strong correlation between anti-alpha-1,6-glucan-IgG levels and anti-perinuclear factor (r=0.642; p < 0.05) in RA patients or anti-nuclear antibodies (r=0.675; p < 0.05) in SLE patients was observed. No significant differences in anti-alpha-1,6-glucan-IgA or-IgM levels were noted between different groups. We conclude that anti-alpha-1,6-glucan-IgG levels were significantly elevated in patients with SLE or RA and positively correlated with disease activity.
Research articles
Structural view of the regulatory subunit of aspartate kinase from Mycobacterium tuberculosis
Qingzhu Yang, Kun Yu, Liming Yan, Yuanyuan Li, Cheng Chen, Xuemei Li
2011, 2(9): 745-754. doi: 10.1007/s13238-011-1094-2
The aspartate kinase (AK) from Mycobacterium tuberculosis (Mtb) catalyzes the biosynthesis of aspartate family amino acids, including lysine, threonine, isoleucine and methionine. We determined the crystal structures of the regulatory subunit of aspartate kinase from Mtb alone (referred to as MtbAKβ) and in complex with threonine (referred to as MtbAKβ-Thr) at resolutions of 2.6 Å and 2.0 Å, respectively. MtbAKβ is composed of two perpendicular non-equivalent ACT domains[aspartate kinase, chorismate mutase, and TyrA (prephenate dehydrogenase)] per monomer. Each ACT domain contains two α helices and four antiparallel β strands. The structure of MtbAKβ shares high similarity with the regulatory subunit of the aspartate kinase from Corynebacterium glutamicum (referred to as CgAKβ), suggesting similar regulatory mechanisms. Biochemical assays in our study showed that MtbAK is inhibited by threonine. Based on crystal structure analysis, we discuss the regulatory mechanism of MtbAK.
The role of the CNOT1 subunit of the CCR4-NOT complex in mRNA deadenylation and cell viability
Kentaro Ito, Akinori Takahashi, Masahiro Morita, Toru Suzuki, Tadashi Yamamoto
2011, 2(9): 755-763. doi: 10.1007/s13238-011-1092-4
The human CCR4-NOT deadenylase complex consists of at least nine enzymatic and non-enzymatic subunits. Accumulating evidence suggests that the non-enzymatic subunits are involved in the regulation of mRNA deadenylation, although their precise roles remain to be established. In this study, we addressed the function of the CNOT1 subunit by depleting its expression in HeLa cells. Flow cytometric analysis revealed that the sub G1 fraction was increased in CNOT1-depleted cells. Virtually, the same level of the sub G1 fraction was seen when cells were treated with a mixture of siRNAs targeted against all enzymatic subunits, suggesting that CNOT1 depletion induces apoptosis by destroying the CCR4-NOT-associated deadenylase activity. Further analysis revealed that CNOT1 depletion leads to a reduction in the amount of other CCR4-NOT subunits. Importantly, the specific activity of the CNOT6L immunoprecipitates-associated deadenylase from CNOT1-depleted cells was less than that from control cells. The formation of P-bodies, where mRNA decay is reported to take place, was largely suppressed in CNOT1-depleted cells. Therefore, CNOT1 has an important role in exhibiting enzymatic activity of the CCR4-NOT complex, and thus is critical in control of mRNA deadenylation and mRNA decay. We further showed that CNOT1 depletion enhanced CHOP mRNA levels and activated caspase-4, which is associated with endoplasmic reticulum ER stress-induced apoptosis. Taken together, CNOT1 depletion structurally and functionally deteriorates the CCR4-NOT complex and induces stabilization of mRNAs, which results in the increment of translation causing ER stress-mediated apoptosis. We conclude that CNOT1 contributes to cell viability by securing the activity of the CCR4-NOT deadenylase.
Spikes with short inter-spike intervals in frog retinal ganglion cells are more correlated with their adjacent neurons' activities
Wen-Zhong Liu, Ru-Jia Yan, Wei Jing, Hai-Qing Gong, Pei-Ji Liang
2011, 2(9): 764-771. doi: 10.1007/s13238-011-1091-5
Correlated firings among neurons have been extensively investigated; however, previous studies on retinal ganglion cell (RGC) population activities were mainly based on analyzing the correlated activities between the entire spike trains. In the present study, the correlation properties were explored based on burst-like activities and solitary spikes separately. The results indicate that:(1) burst-like activities were more correlated with other neurons' activities; (2) burst-like spikes correlated with their neighboring neurons represented a smaller receptive field than that of correlated solitary spikes. These results suggest that correlated burst-like spikes should be more efficient in signal transmission, and could encode more detailed spatial information.