Quality-Control Mechanism for Telomerase RNA Folding in the Cell

Cell Rep. 2020 Dec 29;33(13):108568. doi: 10.1016/j.celrep.2020.108568.

Abstract

Long non-coding RNAs can often fold into different conformations. Telomerase RNA, an essential component of the telomerase ribonucleoprotein (RNP) enzyme, must fold into a defined structure to fulfill its function with the protein catalytic subunit (TERT) and other accessory factors. However, the mechanism by which the correct folding of telomerase RNA is warranted in a cell is still unknown. Here we show that La-related protein Pof8 specifically recognizes the conserved pseudoknot region of telomerase RNA and instructs the binding of the Lsm2-8 complex to its mature 3' end, thus selectively protecting the correctly folded RNA from exonucleolytic degradation. In the absence of Pof8, TERT assembles with misfolded RNA and produces little telomerase activity. Therefore, Pof8 plays a key role in telomerase RNA folding quality control, ensuring that TERT only assembles with functional telomerase RNA to form active telomerase. Our finding reveals a mechanism for non-coding RNA folding quality control.

Keywords: DNA replication; La-protein; genome instability; lncRNA; non-coding RNA folding; quality control; reverse transcriptase; ribonucleoprotein assembly; telomerase; telomere.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Catalytic Domain
  • Mutation
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Quality Control
  • RNA / chemistry
  • RNA / genetics*
  • RNA / metabolism*
  • RNA Folding*
  • RNA Recognition Motif Proteins / chemistry
  • RNA Recognition Motif Proteins / genetics
  • RNA Recognition Motif Proteins / metabolism*
  • RNA, Fungal
  • RNA, Long Noncoding / chemistry
  • RNA, Long Noncoding / metabolism
  • RNA-Binding Motifs
  • Ribonucleoproteins, Small Nuclear / chemistry
  • Ribonucleoproteins, Small Nuclear / metabolism*
  • Schizosaccharomyces / chemistry
  • Schizosaccharomyces / enzymology
  • Schizosaccharomyces / physiology*
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Telomerase / biosynthesis*
  • Telomerase / chemistry
  • Telomerase / genetics
  • Telomerase / metabolism

Substances

  • RNA Recognition Motif Proteins
  • RNA, Fungal
  • RNA, Long Noncoding
  • Ribonucleoproteins, Small Nuclear
  • Schizosaccharomyces pombe Proteins
  • pof8 protein, S pombe
  • telomerase RNA
  • RNA
  • Telomerase