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Nonsense-mediated mRNA Decay02:27

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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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NCBP3 positively impacts mRNA biogenesis.

Yuhui Dou1, Isabelle Barbosa2, Hua Jiang3

  • 1Department of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Allé 3, Aarhus 8000, Denmark.

Nucleic Acids Research
|September 22, 2020
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Summary

Nuclear Cap-Binding Protein 3 (NCBP3) does not replace NCBP2 in the nuclear Cap-Binding Complex (CBC). Instead, NCBP3 interacts with the Exon Junction Complex (EJC) and TRanscription and EXport (TREX) complexes to support mRNA expression.

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Area of Science:

  • Molecular Biology
  • Gene Expression Regulation
  • RNA Processing

Background:

  • The nuclear Cap-Binding Complex (CBC) binds the 5'cap of RNA polymerase II transcripts, influencing RNA fate.
  • C17orf85 (NCBP3) was recently proposed as an alternative CBC component, potentially replacing NCBP2.

Purpose of the Study:

  • To investigate the interaction profile of NCBP3 and its role in RNA processing.
  • To determine if NCBP3 forms an alternative CBC or has distinct functions.

Main Methods:

  • Protein-protein interaction screening of NCBP1, NCBP2, and NCBP3.
  • In vitro and in vivo association studies of NCBP3 with EJC and TREX complexes.
  • Analysis of RNA binding profiles and competition assays with ZC3H18.

Main Results:

  • NCBP3 exhibits a distinct interaction profile compared to NCBP1 and NCBP2.
  • NCBP3 primarily interacts with Exon Junction Complex (EJC) and TRanscription and EXport (TREX) complex components.
  • NCBP3 competes with ZC3H18 for RNA binding and positively impacts nuclear export and expression of large transcripts.

Conclusions:

  • NCBP3 does not form an alternative CBC by replacing NCBP2.
  • NCBP3 functions in conjunction with EJC and TREX complexes.
  • NCBP3 plays a role in supporting mRNA expression, nuclear export, and processing of large multi-exonic transcripts.