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HnRNP D activates production of HPV16 E1 and E6 mRNAs by promoting intron retention

Xiaoxu Cui1, Chengyu Hao1, Lijing Gong1,2

  • 1Department of Laboratory Medicine, Lund University, BMC-B13, 221 84 Lund, Sweden.

Nucleic Acids Research
|March 2, 2022
PubMed

Insights

Heterogeneous nuclear ribonucleoprotein D (hnRNP D) inhibits human papillomavirus type 16 (HPV16) mRNA splicing, leading to intron retention. This process impacts HPV gene expression and the development of HPV-associated cancers.

Area of Science:

  • Molecular Biology
  • Virology
  • Cancer Research

Background:

  • Human papillomavirus type 16 (HPV16) is a major cause of cervical and other cancers.
  • The precise mechanisms regulating HPV16 gene expression, particularly mRNA processing, remain incompletely understood.

Purpose of the Study:

  • To elucidate the role of heterogeneous nuclear ribonucleoprotein D (hnRNP D) in the generation of intron-containing HPV16 mRNAs.
  • To investigate how hnRNP D influences HPV16 gene expression and its contribution to HPV-associated cancers.

Main Methods:

  • Investigated the splicing inhibitory function of hnRNP D on HPV16 E1/E2 and E6/E7 mRNAs.
  • Analyzed the interaction of hnRNP D with splicing machinery components and HPV16 RNA.
  • Assessed the impact of hnRNP D on cytoplasmic mRNA levels, translation, and oncoprotein production.

Main Results:

  • hnRNP D acts as a splicing inhibitor for HPV16 E1/E2 and E6/E7 mRNAs, resulting in intron-retained transcripts.
  • hnRNP D binds to HPV16 mRNAs in the cytoplasm, potentially inhibiting their translation.
  • hnRNP D knockdown in cervical cancer cells increased HPV16 E7 oncoprotein production.
  • hnRNP D40 was found to interact with HPV16 mRNAs in cancer cells and keratinocytes.

Conclusions:

  • hnRNP D plays a critical role in regulating HPV16 mRNA splicing and gene expression.
  • hnRNP D contributes to the development of HPV-associated cancers by modulating HPV gene products.

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