Ribonuclease inhibitor and angiogenin system regulates cell type-specific global translation

Sci Adv. 2024 May 31;10(22):eadl0320. doi: 10.1126/sciadv.adl0320. Epub 2024 May 31.

Abstract

Translation of mRNAs is a fundamental process that occurs in all cell types of multicellular organisms. Conventionally, it has been considered a default step in gene expression, lacking specific regulation. However, recent studies have documented that certain mRNAs exhibit cell type-specific translation. Despite this, it remains unclear whether global translation is controlled in a cell type-specific manner. By using human cell lines and mouse models, we found that deletion of the ribosome-associated protein ribonuclease inhibitor 1 (RNH1) decreases global translation selectively in hematopoietic-origin cells but not in the non-hematopoietic-origin cells. RNH1-mediated cell type-specific translation is mechanistically linked to angiogenin-induced ribosomal biogenesis. Collectively, this study unravels the existence of cell type-specific global translation regulators and highlights the complex translation regulation in vertebrates.

MeSH terms

  • Animals
  • Carrier Proteins
  • Cell Line
  • Gene Expression Regulation
  • Humans
  • Mice
  • Organ Specificity
  • Protein Biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ribonuclease, Pancreatic* / genetics
  • Ribonuclease, Pancreatic* / metabolism
  • Ribosomes* / metabolism

Substances

  • angiogenin
  • Ribonuclease, Pancreatic
  • RNH1 protein, human
  • RNA, Messenger
  • Carrier Proteins