SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing

Nucleic Acids Res. 2021 Sep 20;49(16):9424-9443. doi: 10.1093/nar/gkab647.

Abstract

RNA provides the framework for the assembly of some of the most intricate macromolecular complexes within the cell, including the spliceosome and the mature ribosome. The assembly of these complexes relies on the coordinated association of RNA with hundreds of trans-acting protein factors. While some of these trans-acting factors are RNA-binding proteins (RBPs), others are adaptor proteins, and others still, function as both. Defects in the assembly of these complexes results in a number of human pathologies including neurodegeneration and cancer. Here, we demonstrate that Silencing Defective 2 (SDE2) is both an RNA binding protein and also a trans-acting adaptor protein that functions to regulate RNA splicing and ribosome biogenesis. SDE2 depletion leads to widespread changes in alternative splicing, defects in ribosome biogenesis and ultimately complete loss of cell viability. Our data highlight SDE2 as a previously uncharacterized essential gene required for the assembly and maturation of the complexes that carry out two of the most fundamental processes in mammalian cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alternative Splicing / genetics*
  • DNA-Binding Proteins / genetics*
  • Genes, Essential / genetics
  • Humans
  • RNA Splicing / genetics*
  • RNA-Binding Proteins / genetics
  • Ribosomes / genetics*
  • Spliceosomes / genetics

Substances

  • DNA-Binding Proteins
  • RNA-Binding Proteins
  • SDE2 protein, human