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FRG1 is a direct transcriptional regulator of nonsense-mediated mRNA decay genes

Ananya Palo1, Saket Awadhesbhai Patel1, Bibekananda Sahoo1

  • 1National Institute of Science Education and Research, School of Biological Sciences, Bhubaneswar, Odisha 752050, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400094, India.

Genomics
|December 15, 2022
PubMed

Insights

FRG1 protein influences mRNA surveillance by regulating NMD genes. This discovery sheds light on FRG1

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • FRG1 is implicated in Fascioscapulohumeral Muscular Dystrophy and has roles in development and disease.
  • FRG1's involvement in RNA biogenesis and potential as a heterogeneous nuclear ribonucleoprotein (hnRNP) suggests a link to mRNA surveillance pathways.

Purpose of the Study:

  • To investigate the effect of FRG1 on the expression of Nonsense-Mediated Decay (NMD) genes.
  • To elucidate the mechanism by which FRG1 regulates NMD gene expression.

Main Methods:

  • Microarray profiling to assess FRG1's impact on mRNA surveillance and related pathways.
  • Sequence alignment, structural modeling, Electrophoretic Mobility Shift Assay (EMSA), Chromatin Immunoprecipitation quantitative PCR (ChIP-qPCR), and luciferase reporter assays to identify FRG1 binding sites.
  • Analysis of public datasets and quantitative Real-Time PCR (qRT-PCR) to validate FRG1's correlation and effect on NMD gene transcription.

Main Results:

  • FRG1 alters mRNA surveillance, RNA transport, and spliceosome machinery.
  • A conserved 'CTGGG' nucleotide sequence was identified as a FRG1 binding site on core NMD factors.
  • FRG1 expression correlates with NMD gene expression across various tissues, and FRG1 regulates NMD gene transcription.

Conclusions:

  • FRG1 acts as a transcriptional regulator of NMD genes.
  • The findings reveal a novel mechanism for FRG1 in gene expression regulation with potential implications for diseases associated with mRNA surveillance defects.
Keywords:
EJCFRG1FRG1 binding siteNMDRNA biogenesisSpliceosome complexTranscriptional regulatorhnRNP

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