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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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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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Nonsense-mediated mRNA Decay02:27

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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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In vitro Transcription and Capping of Gaussia Luciferase mRNA Followed by HeLa Cell Transfection
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Mille viae in eukaryotic mRNA decapping.

Eugene Valkov1, Stefanie Jonas2, Oliver Weichenrieder1

  • 1Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen, Germany.

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The decapping enzyme DCP2 regulates mRNA decay by removing the mRNA 5'-cap. This study compares DCP2-DCP1 complex structures, revealing multiple pathways for DCP2-mediated mRNA decapping.

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Area of Science:

  • Molecular Biology
  • Biochemistry
  • Structural Biology

Background:

  • Cellular mRNA levels are controlled by transcription and decay rates.
  • mRNA decapping, mediated by the DCP2 enzyme, is a critical, often irreversible, step in mRNA decay.
  • Regulation of DCP2 activity is crucial and involves complex interactions within the decapping network.

Purpose of the Study:

  • To compare distinct crystal structures of the DCP2-DCP1 decapping complex.
  • To investigate alternative substrate recognition modes of the DCP2 catalytic domain.
  • To understand the assembly control of the decapping network.

Main Methods:

  • Comparative analysis of three recent crystal structures of the DCP2-DCP1 complex.
  • Examination of DCP2-DCP1 complexes with substrate analogs and decapping enhancers.
  • Structure-based analysis of decapping network assembly.

Main Results:

  • Three conformationally distinct crystal structures of the DCP2-DCP1 complex were compared.
  • Alternative substrate recognition modes for the DCP2 catalytic domain were discussed.
  • Structure-based insights into decapping network assembly were provided.

Conclusions:

  • DCP2-mediated mRNA decapping can occur through multiple distinct pathways.
  • Conformational control of the DCP2-DCP1 complex and assembly control of the decapping network are key regulatory mechanisms.
  • Understanding these pathways is vital for comprehending mRNA decay regulation.