Growth arrest-specific transcript 5 associated snoRNA levels are related to p53 expression and DNA damage in

Jonathan Krell1, Adam E Frampton2, Reza Mirnezami3

  • 1Division of Cancer, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom.

Plos One
|June 14, 2014
PubMed
Abstract

Insights

DNA damage induces GAS5-derived small nucleolar RNAs (snoRNAs) in a p53-dependent manner, suggesting a role in the p53 DNA damage response. Their use as housekeeping genes in experiments may yield inaccurate results.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • The growth arrest-specific transcript 5 (GAS5) gene encodes a long noncoding RNA (lncRNA) and hosts small nucleolar RNAs (snoRNAs).
  • GAS5 snoRNAs are implicated in cellular processes and cancer, with potential roles in cell survival and oncogenesis.

Purpose of the Study:

  • Investigate the relationship between DNA damage, p53, and GAS5 snoRNAs.
  • Elucidate the role of GAS5 snoRNAs in the DNA damage response, cell survival, and oncogenesis in vitro and in vivo.

Main Methods:

  • Quantitative analysis of GAS5 snoRNA expression following DNA damage.
  • Assessment of p53 and GAS5 snoRNA relationships in cancer cell lines and human colorectal tissues.
  • Biological techniques to explore snoRNA roles in DNA damage response.

Main Results:

  • DNA damage induced GAS5-derived snoRNA expression in a p53-dependent manner in colorectal cancer cells.
  • DICER did not affect GAS5 snoRNA levels; p53 levels correlated with GAS5 snoRNA expression in colorectal tissues.

Conclusions:

  • GAS5-derived snoRNAs are p53-controlled and mediate the p53 response to DNA damage, independent of ribosomal function.
  • GAS5 snoRNAs are not processed by DICER into miRNA-like molecules; their precise function needs further study.
  • Using GAS5 host snoRNAs as housekeeping genes in qPCR for DNA damage studies can lead to inaccurate results.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.0K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
8.5K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
2.3K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
32.1K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.2K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
7.5K