Identification of discrete classes of small nucleolar RNA featuring different ends and RNA binding protein dependency

Nucleic Acids Res. 2014 Sep;42(15):10073-85. doi: 10.1093/nar/gku664. Epub 2014 Jul 29.

Abstract

Small nucleolar RNAs (snoRNAs) are among the first discovered and most extensively studied group of small non-coding RNA. However, most studies focused on a small subset of snoRNAs that guide the modification of ribosomal RNA. In this study, we annotated the expression pattern of all box C/D snoRNAs in normal and cancer cell lines independent of their functions. The results indicate that C/D snoRNAs are expressed as two distinct forms differing in their ends with respect to boxes C and D and in their terminal stem length. Both forms are overexpressed in cancer cell lines but display a conserved end distribution. Surprisingly, the long forms are more dependent than the short forms on the expression of the core snoRNP protein NOP58, thought to be essential for C/D snoRNA production. In contrast, a subset of short forms are dependent on the splicing factor RBFOX2. Analysis of the potential secondary structure of both forms indicates that the k-turn motif required for binding of NOP58 is less stable in short forms which are thus less likely to mature into a canonical snoRNP. Taken together the data suggest that C/D snoRNAs are divided into at least two groups with distinct maturation and functional preferences.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Female
  • Humans
  • MCF-7 Cells
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / physiology*
  • Nucleic Acid Conformation
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • RNA Splicing Factors
  • RNA, Small Nucleolar / chemistry
  • RNA, Small Nucleolar / classification
  • RNA, Small Nucleolar / metabolism*
  • RNA-Binding Proteins / physiology*
  • Repressor Proteins / physiology*
  • Ribonucleoproteins, Small Nucleolar / antagonists & inhibitors
  • Ribonucleoproteins, Small Nucleolar / physiology*

Substances

  • NOP58 protein, human
  • Nuclear Proteins
  • RBFOX2 protein, human
  • RNA Splicing Factors
  • RNA, Small Nucleolar
  • RNA-Binding Proteins
  • Repressor Proteins
  • Ribonucleoproteins, Small Nucleolar