4.3 Article

RIP-seq reveals LINE-1 ORF1p association with p-body enriched mRNAs

Journal

MOBILE DNA
Volume 12, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s13100-021-00233-3

Keywords

LINE-1; L1EM; ORF1p; Prostate cancer; Processing bodies; RNA; Retrotransposition

Funding

  1. National Institutes of Health [R01CA112226, 1F31CA225053-01A1, P01AG051449]
  2. National Cancer Institute, National Institutes of Health [HHSN261200800001E]

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The study reveals higher levels of LINE-1 RNA and non-LINE-1 mRNAs bound by ORF1p in prostate cancer cells, suggesting biological relevance to prostate cancer.
Background Long INterspersed Element-1 (LINE-1) is an autonomous retroelement able to copy-and-paste itself into new loci of the host genome through a process called retrotransposition. The LINE-1 bicistronic mRNA codes for two proteins, ORF1p, a nucleic acid chaperone, and ORF2p, a protein with endonuclease and reverse transcriptase activity. Both proteins bind LINE-1 mRNA in cis and are necessary for retrotransposition. While LINE-1 transcription is usually repressed in most healthy somatic cells through a plethora of mechanisms, ORF1p expression has been observed in nearly 50% of tumors, and new LINE-1 insertions have been documented in a similar fraction of tumors, including prostate cancer. Results Here, we utilized RNA ImmunoPrecipitation (RIP) and the L1EM analysis software to identify ORF1p bound RNA in prostate cancer cells. We identified LINE-1 loci that were expressed in parental androgen sensitive and androgen independent clonal derivatives. In all androgen independent cells, we found higher levels of LINE-1 RNA, as well as unique expression patterns of LINE-1 loci. Interestingly, we observed that ORF1p bound many non-LINE-1 mRNA in all prostate cancer cell lines evaluated, and polyA RNA, and RNA localized in p-bodies were especially enriched. Furthermore, the expression levels of RNAs identified in our ORF1p RIP correlated with RNAs expressed in LINE-1 positive tumors from The Cancer Genome Atlas (TCGA). Conclusion Our results show a significant remodeling of LINE-1 loci expression in androgen independent cell lines when compared to parental androgen dependent cells. Additionally, we found that ORF1p bound a significant amount of non-LINE-1 mRNA, and that the enriched ORF1p bound mRNAs are also amplified in LINE-1 expressing TCGA prostate tumors, indicating the biological relevance of our findings to prostate cancer.

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