tRNA編集複合体ADAT2/3は,がん細胞の成長とコドンバイアスのmRNA翻訳を促進する

Julia Ramirez-Moya¹, Titi Rindi Antika², Qi Liu³

¹Stem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

Journal of molecular biology

|September 4, 2025

まとめ

遺伝子発現に不可欠なアデノシンからイノシン (A-to-I) tRNA編集は,リポサルコマの成長に不可欠です. ADAT2/3酵素をターゲットにすることで癌治療の新たなアプローチが生まれます

科学分野:

分子生物学
癌研究
エピジェネティクス

背景:

移転RNA (tRNA) は,安定性と機能に影響を与える化学的変化を経験する.
tRNAの位置A34でのアデノシンからイノシン (A-to-I) 編集はコドン認識を拡張し,mRNA翻訳に不可欠である.
がんにおける tRNA 編集の役割はこれまで調査されていません.

研究の目的:

特にADAT2/3デアミナーゼ複合体に焦点を当てて,がんにおけるtRNA編集の役割を調査する.
ADAT2/3 がリポサルコマ (LPS) の発症と進行に関与するかどうかを判断する.
ADAT2/3の活性,mRNAの翻訳,および腫瘍形成のメカニズム的関連を解明する.

主な方法:

人間の腫瘍におけるADAT2/3の遺伝子増幅と過剰発現の分析
細胞成長と腫瘍発生性への影響を評価するために,リポサルコマ細胞におけるADAT2の減少.
tRNA 編集活動,mRNA 翻訳効率,タンパク質ホメオスタシスの測定.
ADAT2/3媒介のtRNA編集によるmRNA標的の特定

主要な成果:

ADAT2 / 3遺伝子は,リポサルコマを含む複数の腫瘍タイプで頻繁に増幅または過剰発現します.
リポサーコマ細胞の増殖と腫瘍発生性はADAT2/3 tRNA編集活動に依存しています.
ADAT2の減少は,tRNAの編集が低下し,特定のmRNAの翻訳が低下し,タンパク質ホメオスタシスが破壊されます.
ADAT2は,NNCコドンによる成長促進mRNAの翻訳を促進することによって,腫瘍生成を促進する.

結論:

ADAT2/3媒介のA-to-I tRNA編集は,リポサルコマの発生と進行において重要な役割を果たします.
ADAT2は特定のコードンを解読し,腫瘍性mRNAを翻訳し,それによって腫瘍の成長を促すのに不可欠です.
ADAT2/3はがん治療における有望な新しい治療目標です.

キーワード:

ADAT2 について ADAT3 について編集するイノシン癌についてエピトランスクリプトーム mRNA翻訳 tRNA について

さらに関連する動画

08:50

A Nonsequencing Approach for the Rapid Detection of RNA Editing

Published on: April 21, 2022

2.7K

07:46

An In Vitro Assay to Detect tRNA-Isopentenyl Transferase Activity

Published on: October 8, 2018

7.0K

関連する概念動画

02:23

RNA Editing

9.2K

RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...

9.2K

01:31

Translation

15.5K

Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...

15.5K

03:03

mTOR Signaling and Cancer Progression

3.9K

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...

3.9K

02:26

tRNA Activation

19.9K

Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...

19.9K

02:28

Leaky Scanning

5.2K

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...

5.2K

02:31

Nuclear Export of mRNA

7.8K

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...