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Nonsense-mediated mRNA Decay

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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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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.
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RNA Splicing01:32

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Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
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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 nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
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ZNF143 is regulated through alternative 3'UTR isoforms.

Richard Patryk Ngondo1, Philippe Carbon1

  • 1Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, 15 rue René Descartes, 67084 Strasbourg, France.

Biochimie
|June 22, 2014
PubMed
Summary

The transcription factor ZNF143

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Cellular Processes

Background:

  • ZNF143 is a vital transcription factor regulating metabolism and cell growth.
  • Its expression is tightly controlled, but post-transcriptional regulation remains unelucidated.
  • Understanding ZNF143 regulation is key to comprehending cellular homeostasis.

Purpose of the Study:

  • To investigate post-transcriptional regulation mechanisms of ZNF143.
  • To identify the role of alternative polyadenylation in ZNF143 expression control.
  • To explore the impact of 3'-UTR isoforms on ZNF143 transcript stability and targeting.

Main Methods:

  • Analysis of ZNF143 3'-untranslated regions (3'-UTRs) and alternative polyadenylation.
  • Investigation of miRNA targeting, specifically miR-590-3p, on ZNF143 isoforms.
Keywords:
3′UTRARE elementAlternative polyadenylationNT2D1ZNF143miR-590-3p

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  • Correlation studies in retinoic acid treated teratocarcinoma cells.

    • Main Results:

    • ZNF143 generates distinct 3'-UTR isoforms via alternative polyadenylation.
    • The longest 3'-UTR isoform contains a destabilizing AU-rich element and is targeted by miR-590-3p.
    • A negative correlation between ZNF143 and miR-590-3p levels was observed during teratocarcinoma cell differentiation.
    • Alternative polyadenylation site usage is independent of ZNF143 transcriptional auto-regulation.

    Conclusions:

    • ZNF143 post-transcriptional regulation is mediated by alternative polyadenylation and 3'-UTR isoforms.
    • The long 3'-UTR isoform, targeted by miR-590-3p, plays a significant role in ZNF143 downregulation during differentiation.
    • Alternative polyadenylation of ZNF143 is a distinct regulatory mechanism separate from transcriptional auto-regulation.