TRANSLATIONAL CONTROL OF GENE EXPRESSION BY MRNA SELECTI

mRNA 选择对基因表达的翻译控制

• 批准号: 3283542
• 负责人: ROSEMARY JAGUS
• 金额: $ 8.57万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-12-01 至 1986-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3283542
• 关键词: cell free system; density gradient ultracentrifugation; developmental genetics; early embryonic stage; embryogenic cleavage; fertilization; gel electrophoresis; gene expression; genetic manipulation; genetic translation; germ cells; immunochemistry; messenger RNA; nonmammalian vertebrate embryology; ribosomes; saltwater environment

Qualitative control of translation is an important mechanism for changing the relative abundancies of different proteins. It is achieved by selective regulation of mRNA binding to ribosomes and is a significant feature of the control of gene expression in animal cells. Such control is observed in the shut-off of host protein synthesis by viruses, in the maintenance of the differentiated state, in the response of cells to heat-shock and in the utilization of stored maternal mRNA during early development. Not only is this control of translation a means of short-term regulation of gene expression, but increasing evidence suggests that it may provide fine-tuning on transcription by feed-back inhibition. The mechanism whereby qualitative control is exerted is currently not understood. Conceivable mechanisms include: a) Non-specific changes in the overall rate of protein synthesis caused by changes in the availability of mRNAs, activated small ribosomal subunits, or initiation factors. b) Specific inhibition of mRNA binding to ribosomes by inhibitory factors or product feedback. c) Specific promotion of mRNA binding by stimulatory factors. The present proposal undertakes to study qualitative translational control using histone synthesis in sea urchin eggs and cleavage-stage embryos as a model system. Whether one or all of the above mechanisms are operative will be determined. The sea urchin system is chosen because histone synthesis is known to be subject to translational control and because there are indications that the system exhibits multiple types of mRNA selection processes. Different histone variants are synthesized at different developmental stages, suggestive of a role of the variants in the regulation of gene expression. In view of this, an understanding of translational control of the histone gene family will increase our comprenension of the regulatory mechanisms operative on gene expression during development.

翻译质量控制是翻译变革的重要机制 不同蛋白质的相对丰度。它是通过以下方式实现的 对与核糖体结合的mRNA的选择性调节是一个重要的 动物细胞中基因表达调控的特点。这种控制是 在病毒阻断宿主蛋白质合成的过程中观察到，在 维持分化状态，在细胞对 热休克及其在早期母体基因表达中的作用 发展。这种对翻译的控制不仅是一种短期手段 对基因表达的调控，但越来越多的证据表明，它可能 通过反馈抑制提供对转录的微调。这个 实施质量控制的机制目前还不是 明白了。可以想到的机制包括： A)由以下因素引起的蛋白质合成总体速度的非特异性变化 可获得性的变化，激活的小核糖体亚基， 或启蒙因素。 B)抑制因子对与核糖体结合的mRNA的特异性抑制 或产品反馈。 C)刺激因子对mRNA结合的特异性促进。 本提案致力于研究质的翻译控制 利用海胆卵和卵裂期胚胎中的组蛋白合成作为 模型系统。上述机制中是否有一种或全部是可操作的 将会被确定。选择海胆系统是因为组蛋白 众所周知，合成是受翻译控制的，因为有 是否有迹象表明该系统显示了多种类型的mRNA选择 流程。不同的组蛋白变异体在不同的 发育阶段，暗示了变异体在 基因表达的调控。有鉴于此，对 组蛋白基因家族的翻译控制将增加我们的 基因表达调控机制的研究进展 在开发过程中。