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真核生物には,転写後のmRNAの品質を管理する様々な機構が存在し,遺伝子発現の正確性が保証されている.このmRNAの品質管理システムの分子機構の解明が進められており,mRNA品質管理機構により排除されている変異遺伝子産物をDNAマイクロアレイや次世代シークエンサーといった様々な新しい手法を用いて同定することも可能となってきている.さらに,品質管理機構の分子メカニズムの理解をもとに,その阻害剤の開発も行われており,患者個人に合わせたオーナーメード医療の実現に寄与していくことが期待される.
Eukaryotes have a conserved RNA surveillance mechanism to help maintain correct gene expression. Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance mechanism that detects and degrades mRNAs containing premature termination codons (PTCs) to eliminate potentially harmful C-terminally truncated proteins. If C-terminally truncated proteins retain some of their function and/or PTC-read through produces functional proteins, NMD suppression leads to the phenotypic rescue of certain PTC-related mutations. The mRNA lacking a translation termination codon is recognized by Nonstop mRNA decay (NSD) pathways which eliminate nonstop mRNA. If translation is aberrantly arrested, mRNA degrade through No-go decay (NGD) pathway. Along with other types of quality control of mRNA that occur during each step of mRNA biogenesis (transcription, splicing and transport) these mRNA surveillance mechanisms help to ensue the integrity of gene expression.
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