相关实验视频

Updated: Dec 29, 2025

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling

Published on: October 28, 2014

核糖体蛋白表达和转化失调促进了乳腺癌的转移

Richard Y Ebright¹, Sooncheol Lee¹, Ben S Wittner¹

¹Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.

Science (New York, N.Y.)

|February 8, 2020

概括

研究人员通过研究循环瘤细胞 (CTC) 来确定促进癌症转移的基因. 过度表达核糖体蛋白RPL15增强了瘤的扩散和转化,突出显示了在侵袭性乳腺癌中潜在的治疗点.

科学领域:

癌症学
分子生物学
遗传学

背景情况:

循环瘤细胞 (CTC) 对于癌症转移至关重要,但驱动这一过程的特定基因仍然很大程度上未知.
了解成功形成远程转移的CTC的遗传基础对于开发有效的癌症疗法至关重要.

研究的目的:

通过在CTC中进行全基因组CRISPR激活屏幕来识别促进远程转移的基因.
研究核糖体蛋白L15 (RPL15) 在增强转移潜力和瘤生长中的作用.

主要方法:

在小鼠中使用乳腺癌患者的CTC进行了体内全基因组CRISPR激活选.
利用RNA测序分析患者新分离的CTC的基因表达特征.
量化转移生长和评估蛋白质合成和细胞循环调节.

主要成果:

鉴定了参与核糖体生物发生和转换的基因作为转移的关键驱动因素.
证明过度表达RPL15可显著增加多个器官的转移生长.
发现RPL15可以选择性地增强其他核糖体蛋白和细胞循环调节者的转化.
发现了一组具有高核糖体和蛋白质合成活性的CTC,与增殖,上皮标志物和不良临床结果有关.

结论:

核糖体生物发生和蛋白质合成对于循环瘤细胞的转移潜力至关重要.
RPL15在促进转移生长方面发挥着重要作用,并可作为治疗点.
针对具有增强蛋白质合成特征的攻击性CTC可以提供一种新的策略来抑制乳腺癌的转移性进展.

更多相关视频

Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale

Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale

Published on: May 17, 2014

Polysome Profiling in Leishmania, Human Cells and Mouse Testis

Polysome Profiling in Leishmania, Human Cells and Mouse Testis

Published on: April 8, 2018

相关概念视频

Regulation of Expression at Multiple Steps

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...

Translational Regulation

Translational Regulation

Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...

Regulation of Expression Occurs at Multiple Steps

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...

MicroRNAs

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...

MicroRNAs

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...

Ribosome Profiling

Ribosome Profiling

Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...