Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning.
Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning.
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DOI：
10.1016/j.cell.2011.03.028
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发表时间：
2011-04-29
期刊：
影响因子：
64.5
通讯作者：
Barna M
中科院分区：
文献类型：
--
作者：
Kondrashov N;Pusic A;Stumpf CR;Shimizu K;Hsieh AC;Ishijima J;Shiroishi T;Barna M
历史上，核糖体被认为是一种复杂的核酶，在mRNA翻译中具有组成性而不是调节性能力。在这里，我们确定突变的核糖体蛋白L38（Rpl38）基因在小鼠表现出令人惊讶的组织特异性图案缺陷，包括明显的同源异型转换的轴骨架。在Rp138突变胚胎中，整体蛋白质合成不变，然而同源框mRNA的选择子集的翻译受到干扰。我们的数据表明，RPL 38促进80 S复合物的形成，这些mRNA作为核糖体的调控成分，赋予转录特异性的翻译控制。我们进一步表明，Rp138表达在发生功能丧失表型的胚胎区域中显著富集。出乎意料的是，核糖体蛋白（RP）的表达屏幕显示动态调节的脊椎动物胚胎内的个别RP。总的来说，这些研究结果表明，RP活动可能受到高度调节，赋予一个新的层的特异性基因表达和哺乳动物发育的控制。
Historically, the ribosome has been viewed as a complex ribozyme with constitutive rather than regulatory capacity in mRNA translation. Here we identify mutations of the Ribosomal Protein L38 (Rpl38) gene in mice exhibiting surprising tissue specific patterning defects, including pronounced homeotic transformations of the axial skeleton. In Rpl38 mutant embryos, global protein synthesis is unchanged however the translation of a select subset of Homeobox mRNAs is perturbed. Our data reveal that RPL38 facilitates 80S complex formation on these mRNAs as a regulatory component of the ribosome to confer transcript-specific translational control. We further show that Rpl38 expression is markedly enriched in regions of the embryo where loss-of-function phenotypes occur. Unexpectedly, a ribosomal protein (RP) expression screen reveals dynamic regulation of individual RPs within the vertebrate embryo. Collectively, these findings suggest that RP activity may be highly regulated to impart a new layer of specificity in the control of gene expression and mammalian development.
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影响因子：
64.8
作者：
Dasen, JS;Liu, JP;Jessell, TM
通讯作者：
Jessell, TM
影响因子：
64.5
作者：
Dasen, JS;Tice, BC;Jessell, TM
通讯作者：
Jessell, TM
影响因子：
11.4
作者：
Bellodi, Cristian;Kopmar, Noam;Ruggero, Davide
通讯作者：
Ruggero, Davide
影响因子：
4.6
作者：
Brend, T;Gilthorpe, J;Rigby, PWJ
通讯作者：
Rigby, PWJ
DOI：
10.1073/pnas.91.26.12644
发表时间：
1994-12-20
影响因子：
11.1
作者：
HORAN, GSB;WU, K;BEHRINGER, RR
通讯作者：
BEHRINGER, RR