• BMB Reports
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• 제46권1호
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• pp.9-16
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• 2013

In mammalian cells, aberrant transcripts harboring a premature termination codon (PTC) can be generated by abnormal or inefficient biogenesis of mRNAs or by somatic mutation. Truncated polypeptides synthesized from these aberrant transcripts could be toxic to normal cellular functions. However, mammalian cells have evolved sophisticated mechanisms for monitoring the quality of mRNAs. The faulty transcripts harboring PTC are subject to nonsense-mediated mRNA decay (NMD), nonsense-mediated translational repression (NMTR), nonsense-associated alternative splicing (NAS), or nonsense-mediated transcriptional gene silencing (NMTGS). In this review, we briefly outline the molecular characteristics of each pathway and suggest mRNA quality control mechanisms as a means to regulate normal gene expression.

• BMB Reports
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• 제50권4호
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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.

• Molecules and Cells
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• 제37권1호
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• pp.1-8
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• 2014

Mammalian-cell messenger RNAs (mRNAs) are generated in the nucleus from precursor RNAs (pre-mRNAs, which often contain one or more introns) that are complexed with an array of incompletely inventoried proteins. During their biogenesis, pre-mRNAs and their derivative mRNAs are subject to extensive cis-modifications. These modifications promote the binding of distinct polypeptides that mediate a diverse array of functions needed for mRNA metabolism, including nuclear export, inspection by the nonsense-mediated mRNA decay (NMD) quality-control machinery, and synthesis of the encoded protein product. Ribonucleoprotein complex (RNP) remodeling through the loss and gain of protein constituents before and after pre-mRNA splicing, during mRNA export, and within the cytoplasm facilitates NMD, ensuring integrity of the transcriptome. Here we review the mRNP rearrangements that culminate in detection and elimination of faulty transcripts by mammalian-cell NMD.

• BMB Reports
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• 제56권12호
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• pp.625-632
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• 2023

Nonsense-mediated mRNA decay (NMD) is both a quality control mechanism and a gene regulation pathway. It has been studied for more than 30 years, with an accumulation of many mechanistic details that have often led to debate and hence to different models of NMD activation, particularly in higher eukaryotes. Two models seem to be opposed, since the first requires intervention of the exon junction complex (EJC) to recruit NMD factors downstream of the premature termination codon (PTC), whereas the second involves an EJC-independent mechanism in which NMD factors concentrate in the 3'UTR to initiate NMD in the presence of a PTC. In this review we describe both models, giving recent molecular details and providing experimental arguments supporting one or the other model. In the end it is certainly possible to imagine that these two mechanisms co-exist, rather than viewing them as mutually exclusive.

• Clinical and Experimental Pediatrics
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• 제48권11호
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• pp.1252-1255
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• 2005

TBG 결핍증은 X 염색체 장완의 TBG 유전자의 돌연변이에 의해서 발생하며, 낮은 총 $T_4$와총$T_3$, 정상 유리 $T_4$와 유리 $T_3$, 정상 TSH 농도를 특징으로 한다. 혈청 티록신글로불린 농도에 따라 완전 TBG 결핍증과 부분 TBG 결핍증으로 나눌 수 있으며, 적절하게 진단하지 못하면 불필요한 검사나 치료의 요인이 될 수 있다. 저자들의 완전 TBG 결핍증으로 진단된 2명의 남아에 대하여 TBG 유전자 분석을 시행하였다. 대상아들은 신생아 선별검사에서 측정된 낮은 총 $T_4$ 농도 때문에 내원하였다. 진찰 소견은 정상이었으며, 갑상선 기능 검사 상 유리 $T_4$, TSH 농도는 정상이었다. 방사면역측정법에 의한 혈청 TBG는 측정되지 않았다. 중합효소연쇄반응을 이용하여 4개의 TBG 유전자 엑손을 증폭한 후 자동염기서열분석을 시행하였다. 두 대상아에서 모두 엑손 4의 352번째 codon의 첫 번째 단일 뉴클레오티드 C의 결손에 의한 frameshift 돌연변이로 374번째 codon에 termination codon이 나타난 것을 확인하였다. 대상아의 어머니들에게서는 돌연변이 대립유전자와 정상 대립유전자의 이형접합체를 확인하였다. 한국인 TBG 결핍증의 역학과 유전적 특성을 규명하기 위한 더 광범위한 연구가 필요할 것으로 생각된다.

• 한국작물학회지
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• 제52권4호
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• pp.458-468
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• 2007

To tolerate environmentally adverse conditions such as cold, drought, and salinity, plants often synthesize and accumulate proline in cells as compatible osmolytes. ${\Delta}^1$-Pyrroline-5-carboxylate synthetase(P5CS) catalyzes the rate-limiting step of proline biosynthesis from glutamate. Two complete genes, MtP5CS1 and MtP5CS2, were isolated from the model legume Medicago truncatula by cDNA cloning and bacterial artificial chromosome library screening. Nucleotide sequence analysis showed that both genes consisted of 20 exons and 19 introns. Alignment of the predicted amino acid sequences revealed high similarities with P5CS proteins from other plant species. The two MtP5CS genes were expressed in response to high salt and low temperature treatments. Semi-quantitative reverse transcription-polymerase chain reaction showed that MtP5CS1 was expressed earlier than MtP5CS2, indicating differential regulation of the two genes. To evaluate the reverse genetic effects of nucleotide changes on MtP5CS function, a Targeting Induced Local Lesions in Genomes approach was taken. Three mutants each were isolated for MtP5CS1 and MtP5CS2, of which a P5CS2 nonsense mutant carrying a codon change from arginine to stop was expected to bring translation to premature termination. These provide a valuable genetic resource with which to determine the function of the P5CS genes in environmental stress responses of legume crops.