SINEUP long non-coding RNA acts via PTBP1 and HNRNPK to promote translational initiation assemblies

Nucleic Acids Res. 2020 Nov 18;48(20):11626-11644. doi: 10.1093/nar/gkaa814.

Abstract

SINEUPs are long non-coding RNAs (lncRNAs) that contain a SINE element, and which up-regulate the translation of target mRNA. They have been studied in a wide range of applications, as both biological and therapeutic tools, although the underpinning molecular mechanism is unclear. Here, we focused on the sub-cellular distribution of target mRNAs and SINEUP RNAs, performing co-transfection of expression vectors for these transcripts into human embryonic kidney cells (HEK293T/17), to investigate the network of translational regulation. The results showed that co-localization of target mRNAs and SINEUP RNAs in the cytoplasm was a key phenomenon. We identified PTBP1 and HNRNPK as essential RNA binding proteins. These proteins contributed to SINEUP RNA sub-cellular distribution and to assembly of translational initiation complexes, leading to enhanced target mRNA translation. These findings will promote a better understanding of the mechanisms employed by regulatory RNAs implicated in efficient protein translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytoplasm / metabolism
  • Green Fluorescent Proteins / analysis
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • HEK293 Cells
  • Heterogeneous-Nuclear Ribonucleoprotein K / metabolism*
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism*
  • Humans
  • Peptide Chain Initiation, Translational*
  • Polypyrimidine Tract-Binding Protein / metabolism*
  • RNA, Long Noncoding / metabolism*
  • RNA-Binding Proteins / metabolism

Substances

  • Heterogeneous-Nuclear Ribonucleoprotein K
  • Heterogeneous-Nuclear Ribonucleoproteins
  • PTBP1 protein, human
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • enhanced green fluorescent protein
  • Polypyrimidine Tract-Binding Protein
  • HNRNPK protein, human
  • Green Fluorescent Proteins