ATPase/helicase Prp2およびその共活性化剤 Spp2によるスプライソーム再構成のメカニズム
Rui Bai1,2,3, Ruixue Wan4,2,3, Chuangye Yan5
1Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang Province, China.
Science (New York, N.Y.)
|November 27, 2020
まとめ
スプライソーム再構成酵素 Prp2 は,mRNA前スプライシングに不可欠であり,その機能にはコアクティベーター Spp2 が必要です. 構造的および生化学的研究により,Prp2 がどのようにプレ- mRNA をチャネルを通して転位させ,効率的なスプライシングを保証するかを明らかにした.
科学分野:
- 分子生物学
- 構造生物学
- 生物化学
背景:
- スプライソームの再編成は,前駆者メッセンジャーRNA (pre-mRNA) のスプライシングに不可欠です.
- Prp2のような保存されたアデノシントリフォスファターゼ (ATPase) /ヘリカーゼは,スプライソームの再構築を駆動する.
- スプライシングにおけるATPアゼ/ヘリカゼ機能の基礎となる構造的メカニズムは十分に理解されていません.
研究 の 目的:
- Prp2とその複合体の原子構造を解明する.
- Prp2機能におけるコアクティベーターSpp2の役割を理解する.
- Prp2によるプレ-mRNA転位のメカニズムを明らかにする.
主な方法:
- 原子構造を決定するX線結晶学
- タンパク質とRNAの相互作用と酵素活性の研究のための生化学分析
- 構造誘導機能測定法
主要な成果:
- Prp2,Prp2-Spp2複合体,およびPrp2-ロードされたスプレイスオームの原子構造を決定した.
- Spp2は,スプライソームと安定したPrp2結合およびその機能に不可欠である.
- Prp2はプレ-mRNAを結合するチャネルを使用し,特定の残留物は後方移動を防ぐ.
- ATP結合と水解はPrp2の構造変化を誘導し,一方的なプレ- mRNA転位を誘導する.
結論:
- Spp2は重要な結合体として機能し,Prp2をスプレイスオームに固定します.
- Prp2は,ATPの水解と結合したプレ-mRNA転位のためのチャネルメカニズムを使用します.
- これらの発見は,スプライソームのリモデリングと,そのプリ-mRNAスプライシングへの結合のための構造的基礎を提供します.
関連する概念動画
01:32RNA Splicing
59.4K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
59.4K
02:37Restarting Stalled Replication Forks
6.1K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
6.1K
02:36RNA Polymerase II Accessory Proteins
3.6K
3.6K
02:36RNA Polymerase II Accessory Proteins
10.3K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
10.3K
02:54Nucleosome Remodeling
10.3K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
10.3K
02:18Alternative RNA Splicing
23.9K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
23.9K