Suppr超能文献

真核翻译起始因子 3a(eIF3a)的 C 端区域促进了 mRNA 的募集、扫描,以及与 eIF3j 和 eIF3b RNA 识别基序一起,选择 AUG 起始密码子。

The C-terminal region of eukaryotic translation initiation factor 3a (eIF3a) promotes mRNA recruitment, scanning, and, together with eIF3j and the eIF3b RNA recognition motif, selection of AUG start codons.

机构信息

Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.

出版信息

Mol Cell Biol. 2010 Sep;30(18):4415-34. doi: 10.1128/MCB.00280-10. Epub 2010 Jun 28.

Abstract

The C-terminal domain (CTD) of the a/Tif32 subunit of budding yeast eukaryotic translation initiation factor 3 (eIF3) interacts with eIF3 subunits j/Hcr1 and b/Prt1 and can bind helices 16 to 18 of 18S rRNA, suggesting proximity to the mRNA entry channel of the 40S subunit. We have identified substitutions in the conserved Lys-Glu-Arg-Arg (KERR) motif and in residues of the nearby box6 element of the a/Tif32 CTD that impair mRNA recruitment by 43S preinitiation complexes (PICs) and confer phenotypes indicating defects in scanning and start codon recognition. The normally dispensable CTD of j/Hcr1 is required for its binding to a/Tif32 and to mitigate the growth defects of these a/Tif32 mutants, indicating physical and functional interactions between these two domains. The a/Tif32 CTD and the j/Hcr1 N-terminal domain (NTD) also interact with the RNA recognition motif (RRM) in b/Prt1, and mutations in both subunits that disrupt their interactions with the RRM increase leaky scanning of an AUG codon. These results, and our demonstration that the extreme CTD of a/Tif32 binds to Rps2 and Rps3, lead us to propose that the a/Tif32 CTD directly stabilizes 43S subunit-mRNA interaction and that the b/Prt1-RRM-j/Hcr1-a/Tif32-CTD module binds near the mRNA entry channel and regulates the transition between scanning-conducive and initiation-competent conformations of the PIC.

摘要

酵母真核翻译起始因子 3(eIF3)的 a/Tif32 亚基的 C 端结构域(CTD)与 eIF3 亚基 j/Hcr1 和 b/Prt1 相互作用,并且可以与 18S rRNA 的 16 到 18 号螺旋结合,提示其与 40S 亚基的 mRNA 进入通道接近。我们已经鉴定出 a/Tif32 CTD 中的保守赖氨酸-谷氨酸-精氨酸-精氨酸(KERR)基序和附近盒 6 元件中的残基的取代,这些取代会损害 43S 起始前复合物(PIC)对 mRNA 的招募,并赋予表明扫描和起始密码子识别缺陷的表型。j/Hcr1 的通常非必需的 CTD 对于其与 a/Tif32 的结合以及减轻这些 a/Tif32 突变体的生长缺陷是必需的,这表明这两个结构域之间存在物理和功能相互作用。a/Tif32 CTD 和 j/Hcr1 N 端结构域(NTD)也与 b/Prt1 中的 RNA 识别基序(RRM)相互作用,并且破坏其与 RRM 相互作用的这两个亚基中的突变增加了 AUG 密码子的渗漏扫描。这些结果以及我们证明 a/Tif32 的极端 CTD 与 Rps2 和 Rps3 结合,使我们提出 a/Tif32 CTD 直接稳定 43S 亚基-mRNA 相互作用,并且 b/Prt1-RRM-j/Hcr1-a/Tif32-CTD 模块结合在 mRNA 进入通道附近并调节 PIC 之间的扫描诱导和起始能力之间的转变。

相似文献

3
Interaction of the RNP1 motif in PRT1 with HCR1 promotes 40S binding of eukaryotic initiation factor 3 in yeast.
Mol Cell Biol. 2006 Apr;26(8):2984-98. doi: 10.1128/MCB.26.8.2984-2998.2006.
9
Structural integrity of the PCI domain of eIF3a/TIF32 is required for mRNA recruitment to the 43S pre-initiation complexes.
Nucleic Acids Res. 2014 Apr;42(6):4123-39. doi: 10.1093/nar/gkt1369. Epub 2014 Jan 13.

引用本文的文献

2
Remodelled ribosomal populations synthesize a specific proteome in proliferating plant tissue during cold.
Philos Trans R Soc Lond B Biol Sci. 2025 Mar 6;380(1921):20230384. doi: 10.1098/rstb.2023.0384.
3
Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control.
Cell Rep. 2024 Apr 23;43(4):113976. doi: 10.1016/j.celrep.2024.113976. Epub 2024 Mar 19.
4
JUN mRNA translation regulation is mediated by multiple 5' UTR and start codon features.
PLoS One. 2024 Mar 14;19(3):e0299779. doi: 10.1371/journal.pone.0299779. eCollection 2024.
5
mRNA Translation Regulation is Mediated by Multiple 5' UTR and Start Codon Features.
bioRxiv. 2023 Nov 17:2023.11.17.567602. doi: 10.1101/2023.11.17.567602.
6
Conformational rearrangements upon start codon recognition in human 48S translation initiation complex.
Nucleic Acids Res. 2022 May 20;50(9):5282-5298. doi: 10.1093/nar/gkac283.
7
eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5'-Untranslated Regions.
Front Mol Biosci. 2022 Jan 11;8:787664. doi: 10.3389/fmolb.2021.787664. eCollection 2021.
8
Large-scale movement of eIF3 domains during translation initiation modulate start codon selection.
Nucleic Acids Res. 2021 Nov 18;49(20):11491-11511. doi: 10.1093/nar/gkab908.
9
Reprogramming mRNA Expression in Response to Defect in RNA Polymerase III Assembly in the Yeast .
Int J Mol Sci. 2021 Jul 7;22(14):7298. doi: 10.3390/ijms22147298.

本文引用的文献

3
Comprehensive molecular structure of the eukaryotic ribosome.
Structure. 2009 Dec 9;17(12):1591-1604. doi: 10.1016/j.str.2009.09.015.
4
eIF1 controls multiple steps in start codon recognition during eukaryotic translation initiation.
J Mol Biol. 2009 Nov 27;394(2):268-85. doi: 10.1016/j.jmb.2009.09.017. Epub 2009 Sep 12.
7
Ribosomal position and contacts of mRNA in eukaryotic translation initiation complexes.
EMBO J. 2008 Jun 4;27(11):1609-21. doi: 10.1038/emboj.2008.90. Epub 2008 May 8.
8
Eukaryotic initiation factor (eIF) 1 carries two distinct eIF5-binding faces important for multifactor assembly and AUG selection.
J Biol Chem. 2008 Jan 11;283(2):1094-103. doi: 10.1074/jbc.M708155200. Epub 2007 Nov 1.
10
eIF3j is located in the decoding center of the human 40S ribosomal subunit.
Mol Cell. 2007 Jun 22;26(6):811-9. doi: 10.1016/j.molcel.2007.05.019.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验