LARP1 isoform expression in human cancer cell lines

RNA Biol. 2021 Feb;18(2):237-247. doi: 10.1080/15476286.2020.1744320. Epub 2020 Apr 14.

Abstract

LARP1 is an oncogenic RNA-binding protein required for ribosome biogenesis and cancer cell survival. From published in vitro studies, there is disparity over which of two different LARP1 protein isoforms (termed the long LI-LARP1 and short SI-LARP1) is the canonical. Here, after conducting a series of biochemical and cellular assays, we conclude that LI-LARP1 (NM_033551.3 > NP_056130.2) is the dominantly expressed form. We observe that SI-LARP1 (NM_015315.5> NP_056130.2) is epigenetically repressed and that this repression is evolutionarily conserved in all but a small subclade of mammalian species. As with other LARP family members, there are multiple potential LARP1 mRNA isoforms that appear to be censored within the nucleus. The capacity of the cell to modulate splicing and expression of these apparently 'redundant' mRNAs hints at contextually specific mechanisms of LARP1 expression.

Keywords: LARP1; RNA Binding Proteins; alternative protein isoforms; cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Autoantigens / chemistry
  • Autoantigens / genetics*
  • Autoantigens / metabolism
  • Cell Line, Tumor
  • DNA Methylation
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Humans
  • Multigene Family
  • Organ Specificity
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA / genetics
  • RNA / metabolism
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribonucleoproteins / chemistry
  • Ribonucleoproteins / genetics*
  • Ribonucleoproteins / metabolism
  • SS-B Antigen

Substances

  • Autoantigens
  • Protein Isoforms
  • RNA-Binding Proteins
  • Ribonucleoproteins
  • RNA