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Translational Regulation01:29

Translational Regulation

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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,...
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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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.
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Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
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Riboswitches01:56

Riboswitches

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Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
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RNA Stability01:53

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Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
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Accelerating Responsive RNA Release Through Structural Optimization of Disulfide-Containing Acyl Groups.

Junsong Guo1, Senfeng Zhang2, Tuan-Khoa Kha1

  • 1Department of Chemistry, National University of Singapore, 4 Science Drive 2, Singapore, 117544, Singapore.

Angewandte Chemie (International Ed. in English)
|June 28, 2025
PubMed
Summary
This summary is machine-generated.

A new chemical method uses redox-responsive RNA modification to temporarily block RNA function. Glutathione (GSH) triggers release, restoring biological activity in various RNA types, including messenger RNA (mRNA).

Keywords:
DisulfideGSHPostsynthetic acylationRNARedox‐responsive

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Area of Science:

  • Chemical Biology
  • RNA Therapeutics
  • Biochemistry

Background:

  • Chemical modification of RNA is vital for biological studies and applications.
  • Postsynthetic 2'-OH acylation allows on-demand RNA activation but faces challenges with larger RNAs.

Purpose of the Study:

  • To develop a generalizable redox-responsive RNA modification strategy for functionalizing RNAs of varying lengths.
  • To enable traceless RNA release and restoration of function using endogenous stimuli.

Main Methods:

  • Developed three strategies for postsynthetic acylation introducing disulfide-containing adducts at 2'-OH positions.
  • Utilized glutathione (GSH) to trigger the release of modified RNA.
  • Demonstrated applicability across diverse RNA constructs including synthetic RNA, sgRNA, and mRNA.

Main Results:

  • Successfully introduced multiple disulfide-containing acyl adducts to temporarily inhibit RNA function.
  • Showcased traceless release of RNA and restoration of function upon GSH exposure.
  • Achieved endogenous GSH-responsive restoration of mRNA translation without cytotoxic stimuli.

Conclusions:

  • Presents a simple and broadly applicable method for modifying and modulating RNA function.
  • Structural optimization of acyl groups facilitates RNA release, enhancing versatility.
  • This strategy holds potential for advancing RNA-based therapeutics and research.