Background: The growth arrest-specific transcript 5 gene (GAS5) encodes a long noncoding RNA (lncRNA) and hosts a
number of small nucleolar RNAs (snoRNAs) that have recently been implicated in multiple cellular processes and cancer.
Here, we investigate the relationship between DNA damage, p53, and the GAS5 snoRNAs to gain further insight into the
potential role of this locus in cell survival and oncogenesis both in vivo and in vitro.
Methods: We used quantitative techniques to analyse the effect of DNA damage on GAS5 snoRNA expression and to assess
the relationship between p53 and the GAS5 snoRNAs in cancer cell lines and in normal, pre-malignant, and malignant
human colorectal tissue and used biological techniques to suggest potential roles for these snoRNAs in the DNA damage
response.
Results: GAS5-derived snoRNA expression was induced by DNA damage in a p53-dependent manner in colorectal cancer
cell lines and their levels were not affected by DICER. Furthermore, p53 levels strongly correlated with GAS5-derived snoRNA
expression in colorectal tissue.
Conclusions: In aggregate, these data suggest that the GAS5-derived snoRNAs are under control of p53 and that they have
an important role in mediating the p53 response to DNA damage, which may not relate to their function in the ribosome.
We suggest that these snoRNAs are not processed by DICER to form smaller snoRNA-derived RNAs with microRNA (miRNA)-
like functions, but their precise role requires further evaluation. Furthermore, since GAS5 host snoRNAs are often used as
endogenous controls in qPCR quantifications we show that their use as housekeeping genes in DNA damage experiments
can lead to inaccurate results.