抗原受容体刺激に対するT細胞運命をプログラムするTRA2βの自己調節されたスプライシング
Timofey A Karginov1, Antoine Ménoret1, Nathan K Leclair2,3
1Department of Immunology, School of Medicine, University of Connecticut, UConn Health, Farmington, CT 06030, USA.
まとめ
TRA2β を含む新しい転写後の調節メカニズム
科学分野:
- 免疫学
- 分子生物学
- 遺伝学
背景:
- MHCペプチドに対するT細胞受容体 (TCR) の感受性は,T細胞の運命を決定する上で極めて重要です.
- トランスクリプションの調節だけでは,TCRの感受性の正規モデルを完全に説明することはできません.
- TCRの感受性を理解するために,ポストトランスクリプションの規制メカニズムが調査されています.
研究 の 目的:
- TCRの感受性に影響を与えるポストトランスクリプションの規制メカニズムを特定し,特徴づけること.
- TCRシグナルトランスクリプトの代替スプライシングの役割を調査する.
- T細胞の反応における TRA2β-PE スプライシングの機能を調査する.
主な方法:
- TCRシグナルトランスクリプトの代替スプライシングの分析
- TRA2βで進化的に保存された毒エクソン (PE) の特定.
- マウスとヒトのモデルでのがんと感染中のTRA2β-PEスプライシングの調査.
主要な成果:
- TRA2β- PEスプライシングは,TCRの感受性のポストトランスクリプションのレギュレータとして特定されました.
- TRA2β-PEスプライシングは,TCR誘発のエフェクターT細胞の拡張と機能に不可欠である.
- TRA2β-PEのスキップは,抗原に対するT細胞の反応を高め,再含有は低抗原条件下でのT細胞の生存を促進する.
結論:
- TRA2β-PEスプライシングはTCRの感受性のゲートキーパーであり,T細胞の運命を決定する.
- このメカニズムはTCR遺伝子の再編成により の脊椎動物で進化した.
- この発見は適応性免疫の新たな調節層を明らかにしています
関連する概念動画
Alternative RNA Splicing
21.0K
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...
21.0K
RNA Splicing
56.2K
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...
56.2K
T Cell Activation and Clonal Selection
688
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
688
TGF - β Signaling Pathway
7.3K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.3K
Chromatin Structure Regulates pre-mRNA Processing
7.0K
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...
7.0K
Diversity of Antigen Receptors
541
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
541


