gadd7 (growth arrested DNA-damage inducible gene 7) is a non-coding RNA discovered in the ovaries of the chinese hamster (Cricetulus griseus). Homologs have been identified in the closely related Long-tailed Dwarf Hamster (C. longicaudatus).[1] Although the gene for this RNA contains open reading frames, translation studies found no protein product hence gadd7 has been classified as non-coding RNA.[2][3]
| gadd7 | |
|---|---|
 Conserved secondary structure of gadd7 RNA | |
| Identifiers | |
| Symbol | gadd7 |
| Rfam | RF01800 |
| Other data | |
| RNA type | Gene |
| Domain(s) | Cricetulus |
| PDB structures | PDBe |
This article may be too technical for most readers to understand. (June 2024) |
gadd7 was previously characterised as a hydrogen peroxide-inducible transcript[3] but has more recently been linked with lipotoxicity[1] - where the accumulation of lipids in non-adipose tissue brings about cell death.[4] gadd7 appears to be a key element in the lipotoxicty pathway, when it is knocked out the resulting mutant is much more resistant to oxidative stress.
The proposed mechanism for gadd7's role in lipotoxicity is:[1]
- The lipid palmitate builds to high concentration within a cell
- Reactive oxygen species (ROS) are generated
- This stress induces the expression of gadd7
- A feed-forward mechanism occurs
- ER stress brings about death of the cell
References
edit- ^ a b c Brookheart RT, Michel CI, Listenberger LL, Ory DS, Schaffer JE (March 2009). "The non-coding RNA gadd7 is a regulator of lipid-induced oxidative and endoplasmic reticulum stress". J. Biol. Chem. 284 (12): 7446–7454. doi:10.1074/jbc.M806209200. PMC 2658040. PMID 19150982. Retrieved 2010-07-23.
- ^ Hollander MC, Alamo I, Fornace AJ (May 1996). "A novel DNA damage-inducible transcript, gadd7, inhibits cell growth, but lacks a protein product". Nucleic Acids Res. 24 (9): 1589–1593. doi:10.1093/nar/24.9.1589. PMC 145844. PMID 8649973.
- ^ a b Crawford DR, Schools GP, Salmon SL, Davies KJ (January 1996). "Hydrogen peroxide induces the expression of adapt15, a novel RNA associated with polysomes in hamster HA-1 cells". Arch. Biochem. Biophys. 325 (2): 256–264. doi:10.1006/abbi.1996.0032. PMID 8561505.
- ^ Unger RH (2002). "Lipotoxic diseases". Annu. Rev. Med. 53: 319–336. doi:10.1146/annurev.med.53.082901.104057. PMID 11818477. Retrieved 2010-07-23.
Further reading
edit- Jackman J, Alamo I, Fornace AJ (November 1994). "Genotoxic stress confers preferential and coordinate messenger RNA stability on the five gadd genes". Cancer Res. 54 (21): 5656–5662. PMID 7923213. Retrieved 2010-07-23.
- Mizenina O, Yanushevich Y, Musatkina E, et al. (January 1998). "C-terminal end of v-src protein interacts with peptide coded by gadd7/adapt15-like RNA in two-hybrid system". FEBS Lett. 422 (1): 79–84. Bibcode:1998FEBSL.422...79M. doi:10.1016/S0014-5793(97)01568-8. PMID 9475174. S2CID 40071666.
- Borradaile NM, Buhman KK, Listenberger LL, et al. (February 2006). "A critical role for eukaryotic elongation factor 1A-1 in lipotoxic cell death". Mol. Biol. Cell. 17 (2): 770–778. doi:10.1091/mbc.E05-08-0742. PMC 1356587. PMID 16319173. Retrieved 2010-07-23.
- Mattick JS (April 2009). "The genetic signatures of noncoding RNAs". PLOS Genet. 5 (4): e1000459. doi:10.1371/journal.pgen.1000459. PMC 2667263. PMID 19390609.
- Wang Y, Crawford DR, Davies KJ (August 1996). "adapt33, a novel oxidant-inducible RNA from hamster HA-1 cells". Arch. Biochem. Biophys. 332 (2): 255–260. doi:10.1006/abbi.1996.0340. PMID 8806733.
- Borradaile NM, Han X, Harp JD, Gale SE, Ory DS, Schaffer JE (December 2006). "Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death". J. Lipid Res. 47 (12): 2726–2737. doi:10.1194/jlr.M600299-JLR200. PMID 16960261. Retrieved 2010-07-23.