• Molecules and Cells
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• v.42 no.7
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• pp.523-529
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• 2019

mRNA quality is controlled by multiple RNA surveillance machineries to reduce errors during gene expression processes in eukaryotic cells. Nonsense-mediated mRNA decay (NMD) is a well-characterized mechanism that degrades error-containing transcripts during translation. The ATP-dependent RNA helicase up-frameshift 1 (UPF1) is a key player in NMD that is mostly prevalent in the cytoplasm. However, recent studies on UPF1-RNA interaction suggest more comprehensive roles of UPF1 on diverse forms of target transcripts. Here we used subcellular fractionation and immunofluorescence to understand such complex functions of UPF1. We demonstrated that UPF1 can be localized to the nucleus and predominantly associated with the chromatin. Moreover, we showed that UPF1 associates more strongly with the chromatin when the transcription elongation and translation inhibitors were used. These findings suggest a novel role of UPF1 in transcription elongation-coupled RNA machinery in the chromatin, as well as in translation-coupled NMD in the cytoplasm. Thus, we propose that cytoplasmic UPF1-centric RNA surveillance mechanism could be extended further up to the chromatin-associated UPF1 and co-transcriptional RNA surveillance. Our findings could provide the mechanistic insights on extensive regulatory roles of UPF1 for many cellular RNAs.

• BMB Reports
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• v.50 no.4
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• pp.186-193
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• 2017

In mammals, cap-dependent translation of mRNAs is initiated by two distinct mechanisms: cap-binding complex (CBC; a heterodimer of CBP80 and 20)-dependent translation (CT) and eIF4E-dependent translation (ET). Both translation initiation mechanisms share common features in driving cap- dependent translation; nevertheless, they can be distinguished from each other based on their molecular features and biological roles. CT is largely associated with mRNA surveillance such as nonsense-mediated mRNA decay (NMD), whereas ET is predominantly involved in the bulk of protein synthesis. However, several recent studies have demonstrated that CT and ET have similar roles in protein synthesis and mRNA surveillance. In a subset of mRNAs, CT preferentially drives the cap-dependent translation, as ET does, and ET is responsible for mRNA surveillance, as CT does. In this review, we summarize and compare the molecular features of CT and ET with a focus on the emerging roles of CT in translation.

• Molecules and Cells
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• v.46 no.11
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• pp.664-671
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• 2023

The proper maintenance of mRNA quality that is regulated by diverse surveillance pathways is essential for cellular homeostasis and is highly conserved among eukaryotes. Here, we review findings regarding the role of mRNA quality control in the aging and longevity of Caenorhabditis elegans, an outstanding model for aging research. We discuss the recently discovered functions of the proper regulation of nonsense-mediated mRNA decay, ribosome-associated quality control, and mRNA splicing in the aging of C. elegans. We describe how mRNA quality control contributes to longevity conferred by various regimens, including inhibition of insulin/insulin-like growth factor 1 (IGF-1) signaling, dietary restriction, and reduced mechanistic target of rapamycin signaling. This review provides valuable information regarding the relationship between the mRNA quality control and aging in C. elegans, which may lead to insights into healthy longevity in complex organisms, including humans.

• BMB Reports
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• v.52 no.12
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• pp.671-678
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• 2019

The random V(D)J recombination process ensures the diversity of the primary immunoglobulin (Ig) repertoire. In two thirds of cases, imprecise recombination between variable (V), diversity (D), and joining (J) segments induces a frameshift in the open reading frame that leads to the appearance of premature termination codons (PTCs). Thus, many B lineage cells harbour biallelic V(D)J-rearrangements of Ig heavy or light chain genes, with a productively-recombined allele encoding the functional Ig chain and a nonproductive allele potentially encoding truncated Ig polypeptides. Since the pattern of Ig gene expression is mostly biallelic, transcription initiated from nonproductive Ig alleles generates considerable amounts of primary transcripts with out-of-frame V(D)J junctions. How RNA surveillance pathways cooperate to control the noise from nonproductive Ig genes will be discussed in this review, focusing on the benefits of nonsense- mediated mRNA decay (NMD) activation during B-cell development and detrimental effects of nonsense-associated altered splicing (NAS) in terminally differentiated plasma cells.

• BMB Reports
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• v.42 no.3
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• pp.125-130
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• 2009

Recent advances in RNA biology reveal unexpected diversity and complexity of cellular RNA metabolism. RNA-binding proteins (RBPs) are essential players in RNA metabolism, regulating RNA splicing, transport, surveillance, decay and translation. Aberrant expression of RBPs affects many steps of RNA metabolism, significantly altering expression of RNA. Thus, altered expression and dysfuncting of RBPs are implicated in the development of various diseases including cancer. In this minireview, we briefly describe emerging roles of RBPs as a global coordinator of post-transcriptional steps and altered RBP as a global generator of cancer related RNA alternative splicing. Identification and characterization of the RNA-RBP network would expand the scope of cellular RNA metabolism and provide novel anti-cancer therapeutic targets based on cancer specific RNA-RBP interaction.

• Genomics & Informatics
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• v.13 no.2
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• pp.26-30
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• 2015

nc886 (=vtRNA2-1, pre-miR-886, or CBL3) is a newly identified non-coding RNA (ncRNA) that represses the activity of protein kinase R (PKR). nc886 is transcribed by RNA polymerase III (Pol III) and is intriguingly the first case of a Pol III gene whose expression is silenced by CpG DNA hypermethylation in several types of cancer. PKR is a sensor protein that recognizes evading viruses and induces apoptosis to eliminate infected cells. Like viral infection, nc886 silencing activates PKR and induces apoptosis. Thus, the significance of the nc886:PKR pathway in cancer is to sense and eliminate pre-malignant cells, which is analogous to PKR's role in cellular innate immunity. Beyond this tumor sensing role, nc886 plays a putative tumor suppressor role as supported by experimental evidence. Collectively, nc886 provides a novel example how epigenetic silencing of a ncRNA contributes to tumorigenesis by controlling the activity of its protein ligand.

• Journal of Cancer Prevention
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• v.22 no.4
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• pp.203-210
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• 2017

After transcription, RNAs are always associated with RNA binding proteins (RBPs) to perform biological activities. RBPs can interact with target RNAs in sequence- and structure-dependent manner through their unique RNA binding domains. In development and progression of carcinogenesis, RBPs are aberrantly dysregulated in many human cancers with various mechanisms, such as genetic alteration, epigenetic change, noncoding RNA-mediated regulation, and post-translational modifications. Upon deregulation in cancers, RBPs influence every step in the development and progression of cancer, including sustained cell proliferation, evasion of apoptosis, avoiding immune surveillance, inducing angiogenesis, and activating metastasis. To develop therapeutic strategies targeting RBPs, RNA interference-based oligonucleotides or small molecule inhibitors have been screened based on reduced RBP-RNA interaction and changed level of target RNAs. Identification of binding RNAs with high-throughput techniques and integral analysis of multiple datasets will help us develop new therapeutic drugs or prognostic biomarkers for human cancers.

• BMB Reports
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• v.50 no.4
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• pp.175-185
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• 2017

Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism ensuring the fast decay of mRNAs harboring a premature termination codon (PTC). As a quality control mechanism, NMD distinguishes PTCs from normal termination codons in order to degrade PTC-carrying mRNAs only. For this, NMD is connected to various other cell processes which regulate or activate it under specific cell conditions or in response to mutations, mis-regulations, stresses, or particular cell programs. These cell processes and their connections with NMD are the focus of this review, which aims both to illustrate the complexity of the NMD mechanism and its regulation and to highlight the cellular consequences of NMD inhibition.

• Korean Journal of Veterinary Research
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• v.60 no.1
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• pp.1-7
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• 2020

We investigated the genotypes of Leptospira spp. detected in symptomatic dogs in Thailand. During April to December 2012, 6 out of 41 client-owned dogs were diagnosed with leptospirosis based on polymerase chain reaction tests. All of the infected dogs showed clinical symptoms related to leptospirosis. Direct genotyping of the causative agent of the canine leptospirosis was conducted from the archival DNA samples extracted from urine or blood of those 6 infected dogs. Sequencing of the partial 16S rRNA and lipL32 genes from all samples identified Leptospira (L.) interrogans as the infecting species. Multilocus sequence typing tests were successful for 2 out of 6 samples. The sequence type (ST) was identified as ST50 for both samples where the profile corresponded to L. interrogans species and Bataviae serogroup. The presence of this genotype of Leptospira has never been reported in Thailand. Thus, our findings showed the existence of ST50 L. interrogans serogroup Bataviae and the ability to cause leptospirosis in dogs in Thailand.

• The Plant Pathology Journal
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• v.28 no.3
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• pp.295-298
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• 2012

Genetic diversity among Pseudomonas syringae pv. morsprunorum isolates from Prunus mume in Korea and Japan was investigated by comparative sequence analysis of the 16S rRNA gene. The strains included 24 field isolates recovered from P. mume in Korea along with seven Japanese strains. Two strains isolated from P. salicina in Japan, one strain from P. avium in the United Kingdom, and the pathotype strain were also used for comparison with their 16S rRNA gene sequences. Nearly complete 16S rRNA gene sequences were sequenced in all 35 strains, and three sequence types, designated types I, II and III, were identified. Eleven strains consisting of five Korean isolates, five Japanese strains, and one strain from the United Kingdom belonged to type I, whereas the pathotype strain and another 19 Korean isolates belonged to type III. Another four Japanese strains belonged to type II. Type I showed 98.9% sequence homology with type III. Type I and II had only two heterogeneous bases. The 16S rRNA sequence types were correlated with the races of P. syringae pv. morsprunorum. Type I and II strains belonged to race 1, whereas type III isolates were included in race 2. Sequence analyses of the 16S rRNA gene from P. syringae pv. morsprunorum were useful in identifying the races and can further be used for epidemiological surveillance of this pathogen.