Jin-Wu Nam, Seo-Won Choi, and Bo-Hyun YouMol. Cells 2016; 39(5): 367-374 https://doi.org/10.14348/molcells.2016.0039
Abstract : Since the RNA world hypothesis was proposed, a large number of regulatory noncoding RNAs (ncRNAs) have been identified in many species, ranging from microorganisms to mammals. During the characterization of these newly discovered RNAs, RNAs having both coding and noncoding functions were discovered, and these were considered bifunctional RNAs. The recent use of computational and high-throughput experimental approaches has revealed increasing evidence of various sources of bifunctional RNAs, such as protein-coding mRNAs with a noncoding isoform and long ncRNAs bearing a small open reading frame. Therefore, the genomic diversity of Janus-faced RNA molecules that have dual characteristics of coding and noncoding indicates that the functional roles of RNAs have to be revisited in cells on a genome-wide scale. Such studies would allow us to further understand the complex gene-regulatory network in cells. In this review, we discuss three major genomic sources of bifunctional RNAs and present a handful of examples of bifunctional RNA along with their functional roles.
Heeyoung Seok, Juyoung Ham, Eun-Sook Jang, and Sung Wook ChiMol. Cells 2016; 39(5): 375-381 https://doi.org/10.14348/molcells.2016.0013
Abstract : MicroRNAs (miRNAs) are small non-coding RNAs (∼22 nucleotides) regulating gene expression at the post-transcriptional level. By directing the RNA-induced silencing complex (RISC) to bind specific target mRNAs, miRNA can repress target genes and affect various biological phenotypes. Functional miRNA target recognition is known to majorly attribute specificity to consecutive pairing with seed region (position 2?8) of miRNA. Recent advances in a transcriptome-wide method of mapping miRNA binding sites (Ago HITS-CLIP) elucidated that a large portion of miRNA-target interactions
Soo Hyun Nam, Young Bin Hong, Young Se Hyun, Da Eun Nam, Geon Kwak, Sun Hee Hwang, Byung-Ok Choi, and Ki Wha ChungMol. Cells 2016; 39(5): 382-388 https://doi.org/10.14348/molcells.2016.2288
Abstract : Inherited peripheral neuropathies (IPN), which are a group of clinically and genetically heterogeneous peripheral nerve disorders including Charcot-Marie-Tooth disease (CMT), exhibit progressive degeneration of muscles in the extremities and loss of sensory function. Over 70 genes have been reported as genetic causatives and the number is still growing. We prepared a targeted gene panel for IPN diagnosis based on next generation sequencing (NGS). The gene panel was designed to detect mutations in 73 genes reported to be genetic causes of IPN or related peripheral neuropathies, and to detect duplication of the chromosome 17p12 region, the major genetic cause of CMT1A. We applied the gene panel to 115 samples from 63 non-CMT1A families, and isolated 15 pathogenic or likely-pathogenic mutations in eight genes from 25 patients (17 families). Of them, eight mutations were unreported variants. Of particular interest, this study revealed several very rare mutations in the
Yura Lee, Kyoung Jun Bae, Hae Jung Chon, Seong Hwan Kim, Soon Ae Kim, and Jiyeon KimMol. Cells 2016; 39(5): 389-394 https://doi.org/10.14348/molcells.2016.2300
Abstract : Dovitinib (TKI258) is a small molecule multi-kinase inhibitor currently in clinical phase I/II/III development for the treatment of various types of cancers. This drug has a safe and effective pharmacokinetic/pharmacodynamic profile. Although dovitinib can bind several kinases at nanomolar concentrations, there are no reports relating to osteoporosis or osteoblast differentiation. Herein, we investigated the effect of dovitinib on human recombinant bone morphogenetic protein (BMP)-2-induced osteoblast differentiation in a cell culture model. Dovitinib enhanced the BMP-2-induced alkaline phosphatase (ALP) induction, which is a representative marker of osteoblast differentiation. Dovitinib also stimulated the translocation of phosphorylated Smad1/5/8 into the nucleus and phosphorylation of mitogen-activated protein kinases, including ERK1/2 and p38. In addition, the mRNA expression of BMP-4, BMP-7, ALP, and OCN increased with dovitinib treatment. Our results suggest that dovitinib has a potent stimulating effect on BMP-2-induced osteoblast differentiation and this existing drug has potential for repositioning in the treatment of bone-related disorders.
Ruthala Kalyani, Ji-Yeon Lee, Hyehyun Min, Heejei Yoon, and Myoung Hee KimMol. Cells 2016; 39(5): 395-402 https://doi.org/10.14348/molcells.2016.2311
Abstract : Identifying Hoxc8 target genes is at the crux of understanding the Hoxc8-mediated regulatory networks underlying its roles during development. However, identification of these genes remains difficult due to intrinsic factors of Hoxc8, such as low DNA binding specificity, context-dependent regulation, and unknown cofactors. Therefore, as an alternative, the present study attempted to test whether the roles of Hoxc8 could be inferred by simply analyzing genes frequently coexpressed with
Dong-Joo You, Cho Rong Park, Sunam Mander, Curie Ahn, Jae Young Seong, and Jong-Ik HwangMol. Cells 2016; 39(5): 403-409 https://doi.org/10.14348/molcells.2016.2320
Abstract : NME1 is a well-known metastasis suppressor which has been reported to be downregulated in some highly aggressive cancer cells. Although most studies have focused on NME1, the NME1 gene also encodes the protein (NME1L) containing N-terminal 25 extra amino acids by alternative splicing. According to previous studies, NME1L has potent anti-metastatic activity, in comparison with NME1, by interacting with IKKβ and regulating its activity. In the present study, we tried to define the role of the N-terminal 25 amino acids of NME1L in NF-κB activation signaling. Unfortunately, the sequence itself did not interact with IKKβ, suggesting that it may be not enough to constitute the functional structure. Further construction of NME1L fragments and biochemical analysis revealed that N-terminal 84 residues constitute minimal structure for homodimerization, IKKβ interaction and regulation of NF-κB signaling. The inhibitory effect of the fragment on cancer cell migration and NF-κB-stimulated gene expression was equivalent to that of whole NME1L. The data suggest that the N-terminal 84 residues may be a core region for the anti-metastatic activity of NME1L. Based on this result, further structural analysis of the binding between NME1L and IKKβ may help in understanding the anti-metastatic activity of NME1L and provide direction to NME1L and IKKβ-related anti-cancer drug design.
Xiaojing Xia, Yanyi Che, Yuanyuan Gao, Shuang Zhao, Changjin Ao, Hongjian Yang, Juxiong Liu, Guowen Liu, Wenyu Han, Yuping Wang, and Liancheng LeiMol. Cells 2016; 39(5): 410-417 https://doi.org/10.14348/molcells.2016.2358
Abstract : During the lactation cycle of the bovine mammary gland, autophagy is induced in bovine mammary epithelial cells (BMECs) as a cellular homeostasis and survival mechanism. Interferon gamma (IFN-γ) is an important antiproliferative and apoptogenic factor that has been shown to induce autophagy in multiple cell lines
Xinxin Wang, Shanshan Ma, Nan Meng, Ning Yao, Kun Zhang, Qinghua Li, Yanting Zhang, Qu Xing, Kang Han, Jishi Song, Bo Yang, and Fangxia GuanMol. Cells 2016; 39(5): 418-425 https://doi.org/10.14348/molcells.2016.2345
Abstract : Resveratrol (RES) plays a critical role in the fate of cells and longevity of animals via activation of the sirtuins1 (SIRT1) gene. In the present study, we intend to investigate whether RES could promote the self-renewal and neural-lineage differentiation in human umbilical cord derived MSCs (hUC-MSCs)
Raksha Singh, Sarmina Dangol, Yafei Chen, Jihyun Choi, Yoon-Seong Cho, Jea-Eun Lee, Mi-Ok Choi, and Nam-Soo JwaMol. Cells 2016; 39(5): 426-438 https://doi.org/10.14348/molcells.2016.0094
Abstract : Plant disease resistance occurs as a hypersensitive response (HR) at the site of attempted pathogen invasion. This specific event is initiated in response to recognition of pathogen-associated molecular pattern (PAMP) and subsequent PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI). Both PTI and ETI mechanisms are tightly connected with reactive oxygen species (ROS) production and disease resistance that involves distinct biphasic ROS production as one of its pivotal plant immune responses. This unique oxidative burst is strongly dependent on the resistant cultivars because a monophasic ROS burst is a hallmark of the susceptible cultivars. However, the cause of the differential ROS burst remains unknown. In the study here, we revealed the plausible underlying mechanism of the differential ROS burst through functional understanding of the