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U6 snRNA m6A メチルトランスファーゼ METTL16 SAMシンセテーゼ イントロンの保持を調節する
Kathryn E Pendleton1, Beibei Chen2, Kuanqing Liu3
1Department of Microbiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Cell
|May 20, 2017
まとめ
メチルトランスフェラーゼMETTL16は,代替スプライシングを制御することによって,SAM合成酵素 (MAT2A) の発現を調節する. このメカニズムは,細胞のS-アデノシルメチオニン (SAM) ホメオスタシスを維持するのに役立ち,METTL16はU6 snRNAをメチル化します.
科学分野:
- 分子生物学
- 遺伝子規制
- RNA 生物学
背景:
- S-アデノシルメチオニンは多くの生物学的プロセスに不可欠です.
- METTL16は,既知の役割を持つN6-アデノシンメチルトランスフェラーゼである.
- SAM合成酵素 (MAT2A) 発現の調節は,細胞内のSAMレベルに不可欠である.
研究 の 目的:
- MAT2A発現の調節におけるMETTL16の役割を調査する.
- SAMレベルがMAT2A発現に影響を与えるメカニズムを解明する.
- U6 spliceosomal小核RNA (snRNA) の修飾におけるMETTL16の機能を特定する.
主な方法:
- 遺伝子発現とスプライシングの分析
- タンパク質とRNAの相互作用を決定するRNA免疫降水 (RIP) 測定法.
- インビトロメチル化試験
- セルラーSAMレベル測定
主要な成果:
- METTL16は,保持されたイントロンの代替スプライシングを通じて,ヒトのMAT2A発現を調節する.
- SAMの枯渇は,METTL16依存のヘアピン構造のMAT2A 3' UTRによるMAT2A発現を誘導する.
- METTL16は,U6 snRNAのメチルトランスファーゼとして識別されます.
- MAT2A 3' UTRのMETTL16占有量が増加すると,スプライシングが促進される.
結論:
- METTL16はSAMホメオスタシスとU6 snRNAの改変を調節する二重の役割を担っています.
- N6-アデノシンメチルトランスフェラーゼMETTL16は,SAMの調節において脊椎動物特有の機能を進化させた.
- MAT2AのMETTL16媒介のスプライシングは,ストレス下での細胞のSAMレベルを維持するための重要なメカニズムです.
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