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Related Concept Videos

RNA Stability01:53

RNA Stability

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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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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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The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
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pre-mRNA Processing02:01

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In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
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Exploring m6A and m5C Epitranscriptomes upon Viral Infection: an Example with HIV
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The structure and function of YTHDF epitranscriptomic m6A readers.

Vilbert Sikorski1, Simona Selberg2, Maciej Lalowski3

  • 1Faculty of Medicine, Department of Pharmacology, University of Helsinki, Finland.

Trends in Pharmacological Sciences
|April 17, 2023
PubMed
Summary
This summary is machine-generated.

N6-methyladenosine (m6A) RNA modifications regulate gene expression. Reader proteins like YTHDF1-3 (DF1-DF3) are key therapeutic targets for diseases like cancer, prompting research into their functions and structures for drug design.

Keywords:
RNA modificationsYTHDFallosteric regulationdrug developmentepitranscriptomicshigher-order cooperativityliquid–liquid phase separationm(6)A reader proteinsoligonucleotide therapeuticspost-transcriptional modificationsselective inhibition

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Drug Discovery

Background:

  • N6-methyladenosine (m6A) is a crucial RNA modification regulating gene expression post-transcriptionally.
  • The balance of m6A levels is controlled by 'writer' and 'eraser' enzymes, with 'reader' proteins mediating its effects.
  • Dysregulation of m6A pathways is implicated in various human diseases, including cancer and inflammatory conditions.

Purpose of the Study:

  • To elucidate the functional roles and molecular mechanisms of m6A reader proteins, specifically YTHDF1-3 (DF1-DF3).
  • To explore DF1-DF3 as emerging therapeutic targets for m6A-mediated pathological processes.
  • To provide insights into structure-based drug design for selective inhibition of DF paralogs.

Main Methods:

  • Review of existing literature on m6A reader protein function and mechanisms.
  • Analysis of structural data for DF1-DF3 paralogs.
  • Exploration of structure-activity relationships for potential drug design.

Main Results:

  • YTHDF1-3 proteins play critical roles in regulating the fate of m6A-modified RNA (m6A-RNA).
  • Emerging evidence highlights the involvement of DF1-DF3 in pathological processes such as cancer and inflammation.
  • Structural insights are beginning to emerge, offering potential for targeted drug development.

Conclusions:

  • Understanding the modes of action and structures of DF1-DF3 is vital for advancing therapeutic strategies.
  • DF1-DF3 represent promising targets for developing novel treatments for m6A-related diseases.
  • Structure-guided drug design approaches hold potential for achieving paralog-selective inhibition of these reader proteins.