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相关概念视频

Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

868
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...
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Regulated mRNA Transport02:22

Regulated mRNA Transport

6.2K
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
6.2K
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

22.4K
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...
22.4K
Alternative RNA Splicing02:18

Alternative RNA Splicing

20.9K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
20.9K
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

6.9K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
6.9K
Types of RNA01:23

Types of RNA

63.1K
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
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相关实验视频

Updated: Jun 2, 2025

An Efficient Strategy for Generating Tissue-specific Binary Transcription Systems in Drosophila by Genome Editing
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在合理设计的mRNA中增强细胞类型特异性的生成框架.

Matvei Khoroshkin1,2,3,4, Arsenii Zinkevich5, Elizaveta Aristova5

  • 1Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.

bioRxiv : the preprint server for biology
|January 13, 2025
PubMed
概括
此摘要是机器生成的。

研究人员开发了PARADE,这是一个AI框架,用于设计具有精确细胞类型特异性的高度稳定的信使RNA (mRNA). 这个平台增强了mRNA疗法,提高了稳定性,疗效,并在临床前模型中减少瘤生长.

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TRAP-rc, Translating Ribosome Affinity Purification from Rare Cell Populations of Drosophila Embryos
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Isolate Cell-Type-Specific RNAs from Snap-Frozen Heterogeneous Tissue Samples without Cell Sorting
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相关实验视频

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TRAP-rc, Translating Ribosome Affinity Purification from Rare Cell Populations of Drosophila Embryos
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科学领域:

  • 分子生物学分子生物学
  • 生物工程是生物工程.
  • 人工智能的人工智能

背景情况:

  • 使者RNA (mRNA) 疗法通过使细胞产生治疗性蛋白质,为疾病治疗提供了前景.
  • 目前面临的挑战包括高稳定性和可编程细胞类型特定传递的工程mRNA.
  • mRNA的未翻译区域 (UTR) 在调节基因表达和稳定性方面发挥着至关重要的作用.

研究的目的:

  • 为设计具有增强稳定性和细胞类型特定活性的mRNA未翻译区域 (UTR) 开发一个计算框架.
  • 为了改进治疗应用,设计新的mRNA序列.
  • 在临床前模型中验证设计的mRNA UTRs的疗效.

主要方法:

  • 在六种细胞类型中测量了6万个5'和3'UTR的调节活性.
  • 开发了PARADE (mRNA UTRs的预测和理性设计),一个生成AI框架.
  • 在细胞系和动物模型中验证了15800个de novo设计的序列.
  • 在瘤模型中对瘤抑制器mRNA (PTEN,P16) 进行了PARADE工程UTR测试.

主要成果:

  • 与现有的RNA疗法相比,PARADE发现了具有优越细胞类型特异性和活性的新型UTR序列.
  • 工程化mRNAs在体内 (肝脏,脏) 显示出强大的组织特异性表达.
  • PARADE增强了mRNA稳定性,导致蛋白质产量增加和治疗耐久性.
  • 在PARADE设计的UTRs显著降低了神经瘤异种移植和正位素小鼠模型中的瘤生长.

结论:

  • PARADE是一个多功能的人工智能平台,用于设计精确,稳定和有效的mRNA疗法.
  • 该框架使mRNA UTRs的合理工程能够用于有针对性的治疗应用.
  • 这种方法有可能促进下一代基于mRNA的药物的开发.