ヒトのU1A snRNPタンパク質は,ポリアデニレーションを,ポリア) ポリメラーゼとの直接的な相互作用によって調節する
S I Gunderson1, K Beyer, G Martin
1European Molecular Biology Laboratory, Gene Expression Programme, Heidelberg, Federal Republic of Germany.
Cell
|February 11, 1994
まとめ
U1Aタンパク質は,独自のプレ-mRNAと結合し,ポリアデニレーションを阻害することによって,その生産を自己調節する. この規則は,哺乳類のポリ・ア・ポリメラーゼ (PAP) との直接の相互作用を伴うが,初期裂解因子を遮断するものではない.
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 処理 RNA 処理
背景:
- U1Aタンパク質は,U1小核リボ核タンパク質 (snRNP) の構成要素である.
- U1Aタンパク質は,そのプレ-mRNAを含むフィードバックメカニズムを通じて,自身の生産を自己調節する.
- U1A自己調節の正確なメカニズムを理解することは,遺伝子発現制御を理解する上で極めて重要です.
研究 の 目的:
- U1Aタンパク質が自己生産を自己調節するインビトロメカニズムを解明する.
- U1A媒介によるポリアデニレーションの阻害に関与する特定の分子相互作用を調査する.
- U1A媒介によるポリアデニレーションの阻害に起因するドメインを特定する.
主な方法:
- 精製されたタンパク質とプレ-mRNAを用いたインビトロ生化学測定法.
- 哺乳類および酵母類のポリアデニレーション反応の分析 哺乳類および酵母類のポリアデニレーション反応の分析 哺乳類および酵母類のポリアデニレーション反応の分析 哺乳類および酵母類のポリアデニレーション反応の分析 哺乳類および酵母類のポリアデニレーション反応の分析
- サイト・ディレクテッド・ミュータゲネシスで,U1Aタンパク質とPAPの機能ドメインを特定する.
主要な成果:
- U1Aタンパク質がそのプレ-mRNAに結合すると,哺乳類のPAPによるポリアデニレーションを阻害するが,酵母PAPによるポリアデニレーションは阻害されない.
- U1Aタンパク質は,割れ分とポリアデニレーション特異性因子 (CPSF) の結合,またはプレ-mRNA割れ分を防ぐことはできません.
- U1Aタンパク質と哺乳類のPAPの間の特定の相互作用は,この相互作用を媒介する識別されたドメインと in vitro で実証されました.
結論:
- U1Aタンパク質の自己調節は,哺乳類のpoly (A) ポリメラーゼの活性を直接抑制することによって媒介される.
- このメカニズムは,初期プリ-mRNA処理因子への干渉ではなく,特定のタンパク質-タンパク質相互作用を伴う.
- U1Aタンパク質は,自身のプレ-mRNAを超えてポリアデニレーションを調節する上でより広範な役割を果たす可能性があります.
関連する概念動画
RNA Splicing
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...
Eukaryotic RNA Polymerases
RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
All three eukaryotic RNAPs require specific transcription factors, of which the...
All three eukaryotic RNAPs require specific transcription factors, of which the...
RNA Polymerase II Accessory Proteins
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...
Chromatin Structure Regulates pre-mRNA Processing
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
Nonsense-mediated mRNA Decay
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
RNA Editing
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...


