2015 Vol. 6, No. 12

“I make efforts, people make comments”: Prof. H. Zanyin Gaw-pioneering the world, the trailblazer and founder of China's virology research
Huan Liu, Han Zhang, Doudou Chen
2015, 6(12): 859-861. doi: 10.1007/s13238-015-0227-4
A peep into mitochondrial disorder: multifaceted from mitochondrial DNA mutations to nuclear gene modulation
Chao Chen, Ye Chen, Min-Xin Guan
2015, 6(12): 862-870. doi: 10.1007/s13238-015-0175-z
Mitochondrial genome is responsible for multiple human diseases in a maternal inherited pattern, yet phenotypes of patients in a same pedigree frequently vary largely. Genes involving in epigenetic modification, RNA processing, and other biological pathways, rather than "threshold effect" and environmental factors, provide more specific explanation to the aberrant phenotype. Thus, the double hit theory, mutations both in mitochondrial DNA and modifying genes aggravating the symptom, throws new light on mitochondrial dysfunction processes. In addition, mitochondrial retrograde signaling pathway that leads to reconfiguration of cell metabolism to adapt defects in mitochondria may as well play an active role. Here we review selected examples of modifier genes and mitochondrial retrograde signaling in mitochondrial disorders, which refine our understanding and will guide the rational design of clinical therapies.
An intriguing RNA species-perspectives of circularized RNA
Ting Shen, Miao Han, Gang Wei, Ting Ni
2015, 6(12): 871-880. doi: 10.1007/s13238-015-0202-0
Circular RNAs (circRNAs), a kind of covalently closed RNA molecule, were used to be considered a type of byproducts of mis-splicing events and were discovered sporadically due to the technological limits in the early years. With the great technological progress such as high-throughput next-generation sequencing, numerous circRNAs have recently been detected in many species. CircRNAs were expressed in a spatio-temporally specific manner, suggesting their regulatory functional potentials were overlooked previously. Intriguingly, some circRNAs were indeed found with critical physiological functions in certain circumstances. CircRNAs have a more stable molecular structure that can resist to exoribonuclease comparing to those linear ones, and their molecular functions include microRNA sponge, regulatory roles in transcription, mRNA traps that compete with linear splicing, templates for translation and possibly other presently unknown roles. Here, we review the discovery and characterization of circRNAs, the origination and formation mechanism, the physiological functions and the molecular roles, along with the methods for detection of circRNAs. We further look into the future and propose key questions to be answered for these magical RNA molecules.
Research articles
MiR-33a suppresses breast cancer cell proliferation and metastasis by targeting ADAM9 and ROS1
Chuankai Zhang, Yunda Zhang, Weiji Ding, Yancheng Lin, Zhengjie Huang, Qi Luo
2015, 6(12): 881-889. doi: 10.1007/s13238-015-0223-8
MicroRNAs (miRNAs) are small noncoding RNAs that have a pivotal role in the post-transcriptional regulation of gene expression by sequence-specifically targeting multiple mRNAs. Although miR-33a was recently reported to play an important role in lipid homeostasis, atherosclerosis, and hepatic fibrosis, the functions of miR-33a in tumor progression and metastasis are largely unknown. Here, we found that downregulated miR-33a in breast cancer tissues correlates with lymph node metastasis. MiR-33a expression is significantly lower in the highly metastatic breast cancer cell lines than the noncancerous breast epithelial cells and non-metastatic breast cancer cells. Moreover, the overexpression of miR-33a in metastatic breast cancer cells remarkably decreases cell proliferation and invasion in vitro and significantly inhibits tumor growth and lung metastasis in vivo, whereas its knockdown in non-metastatic breast cancer cells significantly enhances cell proliferation and invasion in vitro and promotes tumor growth and lung metastasis in vivo. Combining bioinformatics prediction and biochemical analyses, we showed that ADAM9 and ROS1 are direct downstream targets of miR-33a. These findings identified miR-33a as a negative regulator of breast cancer cell proliferation and metastasis.
Dermal fibroblast expression of stromal cellderived factor-1 (SDF-1) promotes epidermal keratinocyte proliferation in normal and diseased skin
Chunji Quan, Moon Kyun Cho, Yuan Shao, Laurel E. Mianecki, Eric Liao, Daniel Perry, Taihao Quan
2015, 6(12): 890-903. doi: 10.1007/s13238-015-0198-5
Stromal cells provide a crucial microenvironment for overlying epithelium. Here we investigated the expression and function of a stromal cell-specific protein, stromal cell-derived factor-1 (SDF-1), in normal human skin and in the tissues of diseased skin. Immunohistology and laser capture microdissection (LCM)-coupled quantitative realtime RT-PCR revealed that SDF-1 is constitutively and predominantly expressed in dermal stromal cells in normal human skin in vivo. To our surprise, an extremely high level of SDF-1 transcription was observed in the dermis of normal human skin in vivo, evidenced by much higher mRNA expression level than type I collagen, the most abundant and highly expressed protein in human skin. SDF-1 was also upregulated in the tissues of many human skin disorders including psoriasis, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Double immunostaining for SDF-1 and HSP47 (heat shock protein 47), a marker of fibroblasts, revealed that fibroblasts were the major source of stroma-cell-derived SDF-1 in both normal and diseased skin. Functionally, SDF-1 activates the ERK (extracellular-signal-regulated kinases) pathway and functions as a mitogen to stimulate epidermal keratinocyte proliferation. Both overexpression of SDF-1 in dermal fibroblasts and treatment with rhSDF-1 to the skin equivalent cultures significantly increased the number of keratinocyte layers and epidermal thickness. Conversely, the stimulative function of SDF-1 on keratinocyte proliferation was nearly completely eliminated by interfering with CXCR4, a specific receptor of SDF-1, or by knock-down of SDF-1 in fibroblasts. Our data reveal that extremely high levels of SDF-1 provide a crucial microenvironment for epidermal keratinocyte proliferation in both physiologic and pathologic skin conditions.
Analysis of the preferences for splice codes across tissues
Tao Huang, Meng Wang, Yu-Dong Cai
2015, 6(12): 904-907. doi: 10.1007/s13238-015-0226-5
Comparative proteomic analysis of plasma from bipolar depression and depressive disorder: identification of proteins associated with immune regulatory
Jin Chen, ChengLong Huang, YiRen Song, HaiYang Shi, Dong Wu, YongTao Yang, ChengLong Rao, Li Liao, You Wu, JianYong Tang, Ke Cheng, Jian Zhou, Peng Xie
2015, 6(12): 908-911. doi: 10.1007/s13238-015-0218-5
Pathway-based analysis for genome-wide association study data of bipolar disorder provides new insights for genetic study
Suhua Chang, Jinglu Wang, Kunlin Zhang, Jing Wang
2015, 6(12): 912-915. doi: 10.1007/s13238-015-0201-1
Efficient derivation of embryonic stem cells from NOD-scid Il2rg-/- mice
Kang Liu, Riguo Fang, Haibo Li, Weifeng Yang, Zhenchuan Miao, Jinhua Wen, Hongkui Deng
2015, 6(12): 916-918. doi: 10.1007/s13238-015-0209-6
An improved method for phasing crystal structures with low non-crystallographic symmetry using cryo-electron microscopy data
Jia Wang, Weiguang Wang, Wen Song, Zhifu Han, Heqiao Zhang, Jijie Chai, Hongwei Wang, Jiawei Wang
2015, 6(12): 919-923. doi: 10.1007/s13238-015-0219-4
Structural basis for inhibition of the Tob-CNOT7 interaction by a fragment screening approach
Yuwei Bai, Shinya Tashiro, Satoru Nagatoishi, Toru Suzuki, Dongke Yan, Ruihua Liu, Kouhei Tsumoto, Mark Bartlam, Tadashi Yamamoto
2015, 6(12): 924-928. doi: 10.1007/s13238-015-0225-6
Erratum to: hCLP46 increases Smad3 protein stability via inhibiting its ubiquitin-proteasomal degradation
Yingying Xing, Qiaoyun Chu, Run Feng, Wei Wang, Lixin Liu, Zhongbing Lu
2015, 6(12): 929-929. doi: 10.1007/s13238-015-0186-9
Erratum to: Generation of cell-type-specific gene mutations by expressing the sgRNA of the CRISPR system from the RNA polymerase II promoters
Jiaqiang Wang, Xin Li, Yanhua Zhao, Jingyu Li, Qi Zhou, Zhonghua Liu
2015, 6(12): 930-930. doi: 10.1007/s13238-015-0215-8