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Related Concept Videos

Pre-mRNA Processing: Modification of pre-mRNA Ends01:35

Pre-mRNA Processing: Modification of pre-mRNA Ends

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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.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps...
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pre-mRNA Processing02:01

pre-mRNA Processing

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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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Leaky Scanning02:28

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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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Regulation of Expression at Multiple Steps01:23

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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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Co-activators and Co-repressors02:04

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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

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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.
The chromatin structure, especially...
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Structural insights into human co-transcriptional capping.

Gaurika Garg1, Christian Dienemann1, Lucas Farnung1

  • 1Max Planck Institute for Multidisciplinary Sciences, Department of Molecular Biology, Am Fassberg 11, 37077 Göttingen, Germany.

Molecular Cell
|June 27, 2023
PubMed
Summary

Co-transcriptional pre-mRNA capping protects RNA polymerase II transcripts from degradation and immune response. Cryo-EM structures reveal how capping enzymes RNGTT and CMTR1 interact with RNA polymerase II during this essential process.

Keywords:
CMTR1RNA Pol IIRNA polymerase IIRNGTTcappingco-transcriptional cappingco-transcriptional processingmRNA processingtranscriptiontranscription elongation

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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biochemistry

Background:

  • Co-transcriptional capping of messenger RNA (mRNA) is crucial for RNA stability and immune system regulation.
  • Understanding the molecular mechanisms of capping is essential for comprehending gene expression control.

Purpose of the Study:

  • To elucidate the mechanistic steps of human co-transcriptional pre-mRNA capping.
  • To provide structural insights into the interactions between capping enzymes and RNA polymerase II.

Main Methods:

  • Utilized six distinct cryoelectron microscopy (cryo-EM) structures.
  • Analyzed the interactions between capping enzymes (RNGTT, CMTR1) and RNA polymerase II (Pol II).

Main Results:

  • Detailed the sequential docking and positioning of the capping enzyme RNGTT to the Pol II stalk and surface.
  • Showcased the guanylyltransferase activity occurring when RNA reaches approximately 22 nucleotides.
  • Described the binding of methyltransferase CMTR1 for cap(1) methylation when RNA reaches approximately 29 nucleotides.

Conclusions:

  • Mechanistic insights into human co-transcriptional pre-mRNA capping have been provided through cryo-EM structures.
  • Capping factor rearrangements on Pol II are influenced by catalytic steps and accommodated by factors like DSIF.
  • This study enhances our understanding of mRNA processing and its regulation.