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English: General modes and determinants of 3′UTR in post-transcriptional regulation. (A) Schematic illustration of the distinctive features of an eukaryotic mRNA. The 5′-terminal cap structure interacts with the 3′-terminal poly(A) tail of an mRNA through associated eIF4F and PABP. The coding sequence (CDS) is flanked by 5′- and 3′UTR, which harbors cis-regulatory sequences (marked in red) and provides a binding platform for trans-acting factors (green). (B) Translational repression mechanisms. (i) Competition/interference with cap-binding complex, eIF4F (ii) Inhibition of ribosomal subunit joining (iii) Inhibition of translation elongation. (C) Deadenylation and decapping. Recruitment of the CCR4-NOT deadenylase complex by trans-acting factors catalyzes the deadenylation of the mRNA target. This is often followed by the removal of the 5′-terminal cap structure by the decapping factors (DCP1-DCP2), and the associated co-factors. (D) mRNA decay. mRNAs that are deadenylated and decapped are rapidly degraded by either 5′- > 3′ exonuclease (XRN1) or 3′- > 5′ exonuclease (exosome). (E) RNA localization. Translationally repressed mRNAs are transported along the cytoskeleton to which it is tethered by RBPs and motor proteins. Upon reaching its destination, the mRNA is anchored, and its translation is de-repressed.
日本語: 転写後制御における3'UTRの一般的な様式と決定要因。(A) 真核生物のmRNAの顕著な特徴を示す模式図。5'末端キャップ構造は、関連するeIF4FとPABPを介してmRNAの3'末端ポリ(A)テールと相互作用する。コーディング配列 (CDS) は5'UTRと3'UTRに挟まれ、シス調節配列 (赤でマーク) を含み、トランス作用因子 (緑) の結合プラットフォームを提供する。(B) 翻訳抑制機構。(i) キャップ結合複合体eIF4Fとの競合/干渉 (ii) リボソームサブユニット結合の阻害 (iii) 翻訳伸長の阻害。(C) 脱アデニル化と脱キャップ。トランス作用因子によってCCR4-NOTデアデニラーゼ複合体が動員されると、標的mRNAの脱アデニル化を触媒する。この後、デキャッピング因子 (DCP1-DCP2)、および関連する補因子により5'末端キャップ構造が除去されることがよくある。(D) mRNAの分解。脱アデニル化および脱キャップされたmRNAは、5'→3'エキソヌクレアーゼ (XRN1)または3'→5'エキソヌクレアーゼ (エキソソーム) のいずれかによって速やかに分解される。(E) RNAの局在化。翻訳抑制されたmRNAは、RBPとモータータンパク質によって繋がれ、細胞骨格に沿って輸送される。目的地に到達すると、mRNAは固定され、その翻訳抑制は解除される。
Date
Source Mayya VK and Duchaine TF (2019) Ciphers and Executioners: How 3′-Untranslated Regions Determine the Fate of Messenger RNAs. Front. Genet. 10:6. https://doi.org/10.3389/fgene.2019.00006
Author Vinay K. Mayya and Thomas F. Duchaine

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General modes and determinants of 3′UTR in post-transcriptional regulation.

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