ストレスにさらされたヒト細胞におけるマイクロRNA媒介によるトランスレーション抑制の緩和
Suvendra N Bhattacharyya1, Regula Habermacher, Ursula Martine
1Friedrich Miescher Institute for Biomedical Research, P.O. Box 2543, 4002 Basel, Switzerland.
Cell
|June 17, 2006
まとめ
遺伝子発現のマイクロRNA抑制は逆転可能である. ストレス状態では,miR-122の抑制からカチオニックアミノ酸トランスポーター1 (CAT-1) mRNAを放出し,タンパク質の生産を回復させることができます.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝子規制 遺伝子規制
- RNA 生物学 RNA 生物学
背景:
- マイクロRNA (miRNA) は,メタゾアにおける遺伝子発現の重要な調節体である.
- miRNAは通常,標的mRNAの3'未翻訳領域 (3'UTR) に結合し,タンパク質合成を阻害するか,mRNAの分解を促進する.
- miRNA媒介抑制の可逆性は,まだほとんど研究されていない.
研究 の 目的:
- miRNAによって誘発される遺伝子サイレンスが逆行可能なプロセスであるかどうかを調査する.
- 標的mRNAsの潜在的減圧の原因となるメカニズムを特定する.
- ストレス状態がmiRNAの活性を調節する役割を調べる.
主な方法:
- 利用したヒト肝がん細胞.
- miR-122.2によるカチオンアミノ酸トランスポーター1 (CAT-1) mRNAの調節を研究した.
- 雇用されたレポーターは,遺伝子発現を評価するためのアッセイをします.
- ポリソームプロファイリングやRNA結合タンパク質分析などの技術を使用して,mRNAとタンパク質の相互作用の細胞下局部化を調査しました.
主要な成果:
- CAT-1 mRNAとその3'UTRレポーターのmiR-122誘発阻害は,ストレス条件下では逆転することが示された.
- デレプレスされたCAT-1mRNAが処理体から放出され,ポリソームに徴用されることが観察されました.
- HuR (AU豊富な元素結合タンパク質) がCAT-1 3'UTRと結合することが,この脱圧プロセスに不可欠であることを示した.
結論:
- miRNA媒介の遺伝子抑制は必ずしも永久的な状態ではないし,逆転することもできる.
- ストレスによって引き起こされる特定のmRNAsの減圧は,阻害複合体からの放出と,その後の翻訳を含みます.
- 3'UTRと相互作用するHuRのようなタンパク質は,miRNAの有効性を調節することができ,遺伝子発現制御におけるより広範な役割を示唆しています.
関連する概念動画
MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
Regulation of Expression Occurs at Multiple Steps
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
Experimental RNAi
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...


