Intracellular polarization of RNAs and proteins in the human small intestinal epithelium

PLoS Biol. 2024 Dec 2;22(12):e3002942. doi: 10.1371/journal.pbio.3002942. eCollection 2024 Dec.

Abstract

The intestinal epithelium is a polarized monolayer of cells, with an apical side facing the lumen and a basal side facing the blood stream. In mice, both proteins and mRNAs have been shown to exhibit global basal-apical polarization; however, polarization in the human intestine has not been systematically explored. Here, we employed laser-capture microdissection to isolate apical and basal epithelial segments from intestinal tissues of 8 individuals and performed RNA sequencing and mass-spectrometry proteomics. We find a substantial polarization of mRNA molecules that largely overlaps polarization patterns observed in mice. This mRNA polarization remains consistent across different zones of the intestinal villi and is generally correlated with the polarization of proteins. Our protein analysis exposes streamlined intracellular nutrient transport and processing and reveals that mitochondria and ribosomes are less polarized in humans compared to mice. Our study provides a resource for understanding human intestinal epithelial biology.

MeSH terms

  • Animals
  • Cell Polarity
  • Female
  • Humans
  • Intestinal Mucosa* / metabolism
  • Intestine, Small* / cytology
  • Intestine, Small* / metabolism
  • Laser Capture Microdissection / methods
  • Male
  • Mice
  • Mitochondria / metabolism
  • Proteins / genetics
  • Proteins / metabolism
  • Proteomics / methods
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • Ribosomes / metabolism

Substances

  • RNA, Messenger
  • Proteins

Grants and funding

S.I. is supported by the Moross Integrated Cancer Center, the Helen and Martin Kimmel Award for Innovative Investigation, the Yad Abraham Research Center for Cancer Diagnostics and Therapy, the Israel Science Foundation grants no. 908/21 and no. 3663/21, the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme grant no. 768956, a Weizmann-Sheba joint research grant and a research grant from the Ministry of Innovation, Science and Technology, Israel. The funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.