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mRNA 密码子- tRNA 匹配有助于 LARP4 活性，从而保护核糖体蛋白 mRNA 的多（A）尾长度。

mRNA codon-tRNA match contributes to LARP4 activity for ribosomal protein mRNA poly(A) tail length protection.

机构信息

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.

Molecular Genetics Laboratory, National Institute of Immunology, New Delhi, India.

出版信息

Elife. 2017 Sep 12;6:e28889. doi: 10.7554/eLife.28889.

DOI:10.7554/eLife.28889
PMID:28895529
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5626478/
Abstract

Messenger RNA function is controlled by the 3' poly(A) tail (PAT) and poly(A)-binding protein (PABP). La-related protein-4 (LARP4) binds poly(A) and PABP. mRNA contains a translation-dependent, coding region determinant (CRD) of instability that limits its expression. Although the CRD comprises <10% of LARP4 codons, the mRNA levels vary >20 fold with synonymous CRD substitutions that accommodate tRNA dynamics. Separately, overexpression of the most limiting tRNA increases LARP4 levels and reveals its functional activity, net lengthening of the PATs of heterologous mRNAs with concomitant stabilization, including ribosomal protein (RP) mRNAs. Genetic deletion of cellular LARP4 decreases PAT length and RPmRNA stability. This LARP4 activity requires its PABP-interaction domain and the RNA-binding module which we show is sensitive to poly(A) 3'-termini, consistent with protection from deadenylation. The results indicate that LARP4 is a posttranscriptional regulator of ribosomal protein production in mammalian cells and suggest that this activity can be controlled by tRNA levels.

摘要

信使 RNA 的功能受 3' 聚（A）尾 (PAT) 和多聚（A）结合蛋白 (PABP) 控制。La 相关蛋白-4 (LARP4) 结合 poly(A) 和 PABP。mRNA 含有一个依赖翻译的不稳定性编码区决定因素 (CRD)，限制其表达。尽管 CRD 包含 <10%的 LARP4 密码子，但同义 CRD 取代会导致 mRNA 水平变化超过 20 倍，从而适应 tRNA 动力学。另外，最具限制性的 tRNA 的过表达会增加 LARP4 水平并揭示其功能活性，即异源 mRNA 的 PAT 净延长，同时伴随稳定，包括核糖体蛋白 (RP) mRNA。细胞 LARP4 的遗传缺失会缩短 PAT 长度并降低 RPmRNA 的稳定性。这种 LARP4 活性需要其 PABP 相互作用域和 RNA 结合模块，我们发现该模块对 poly(A) 3'-末端敏感，与脱腺苷酸化保护一致。结果表明，LARP4 是哺乳动物细胞中核糖体蛋白产生的转录后调节剂，并表明该活性可通过 tRNA 水平进行控制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/a30dcc60fb14/elife-28889-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/389f50431541/elife-28889-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/0e200305e32a/elife-28889-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/fbf7f34349ba/elife-28889-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/7e91eb0e8fc8/elife-28889-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/ead147fbe147/elife-28889-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/caf658784b6b/elife-28889-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/2318f8cbbf71/elife-28889-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/8badb61060cb/elife-28889-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/5809ba4b4caa/elife-28889-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/dd30e629c6d4/elife-28889-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/fd1659eee2cb/elife-28889-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/a30dcc60fb14/elife-28889-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/389f50431541/elife-28889-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/0e200305e32a/elife-28889-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/fbf7f34349ba/elife-28889-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/7e91eb0e8fc8/elife-28889-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/ead147fbe147/elife-28889-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/caf658784b6b/elife-28889-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/2318f8cbbf71/elife-28889-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/8badb61060cb/elife-28889-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/5809ba4b4caa/elife-28889-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/dd30e629c6d4/elife-28889-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/fd1659eee2cb/elife-28889-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96b/5626478/a30dcc60fb14/elife-28889-fig9.jpg

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